@misc{london_watterson_mergler_albin_andrade-rivas_di ciaula_comba_giannasi_habib_hay_et al._2024, title={A call from 40 public health scientists for an end to the continuing humanitarian and environmental catastrophe in Gaza}, volume={23}, ISSN={["1476-069X"]}, DOI={10.1186/s12940-024-01097-9}, abstractNote={Abstract An under-recognised aspect of the current humanitarian catastrophe in Gaza is the impact of the war on the environment and the associated risks for human health. This commentary contextualises these impacts against the background of human suffering produced by the overwhelming violence associated with the use of military force against the general population of Gaza. In calling for an immediate cessation to the violence, the authors draw attention to the urgent need to rebuild the health care system and restore the physical and human infrastructure that makes a liveable environment possible and promotes human health and well-being, especially for the most vulnerable in the population. Environmental remediation should therefore form one of the most important parts of international efforts to assist reconstruction, through which we hope Palestinians and Israelis will achieve lasting peace, health, and sustainable development, all as part of accepted international human rights obligations.}, number={1}, journal={ENVIRONMENTAL HEALTH}, author={London, Leslie and Watterson, Andrew and Mergler, Donna and Albin, Maria and Andrade-Rivas, Federico and Di Ciaula, Agostino and Comba, Pietro and Giannasi, Fernanda and Habib, Rima R. and Hay, Alastair and et al.}, year={2024}, month={Jun} } @article{kotlarz_mccord_wiecha_weed_cuffney_enders_strynar_knappe_reich_hoppin_2024, title={Measurement of Hydro-EVE and 6:2 FTS in Blood from Wilmington, North Carolina, Residents, 2017-2018}, volume={132}, ISSN={["1552-9924"]}, url={https://doi.org/10.1289/EHP14503}, DOI={10.1289/EHP14503}, number={2}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Wiecha, Nate and Weed, Rebecca A. and Cuffney, Michael and Enders, Jeffrey R. and Strynar, Mark and Knappe, Detlef R. U. and Reich, Brian J. and Hoppin, Jane A.}, year={2024}, month={Feb} } @article{joode_penaloza-castaneda_mora_corrales-vargas_eskenazi_hoppin_lindh_2024, title={Pesticide exposure, birth size, and gestational age in the ISA birth cohort, Costa Rica}, volume={8}, ISSN={["2474-7882"]}, url={https://doi.org/10.1097/EE9.0000000000000290}, DOI={10.1097/EE9.0000000000000290}, abstractNote={Purpose: To examine associations of prenatal biomarkers of pesticide exposure with birth size measures and length of gestation among newborns from the Infants’ Environmental Health (ISA) birth cohort, Costa Rica. Methods: We included 386 singleton liveborn newborns with data on birth size measures, length of gestation, and maternal urinary biomarkers of chlorpyrifos, synthetic pyrethroids, mancozeb, pyrimethanil, and 2, 4-D during pregnancy. We associated biomarkers of exposure with birth outcomes using multivariate linear regression and generalized additive models. Results: Concentrations were highest for ethylene thiourea (ETU, metabolite of mancozeb), median = 3.40; p10–90 = 1.90–6.79 µg/L, followed by 3,5,6-trichloro-2-pyridinol (TCP, metabolite of chlorpyrifos) p50 = 1.76 p10–90 = 0.97–4.36 µg/L, and lowest for 2,4-D (p50 = 0.33 p10–90 = 0.18–1.07 µg/L). Among term newborns (≥37 weeks), higher prenatal TCP was associated with lower birth weight and smaller head circumference (e.g., β per 10-fold-increase) during the second half of pregnancy = −129.6 (95% confidence interval [CI] = −255.8, −3.5) grams, and −0.61 (95% CI = −1.05, −0.17) centimeters, respectively. Also, among term newborns, prenatal 2,4-D was associated with lower birth weight ( β per 10-fold-increase = −125.1; 95% CI = −228.8, −21.5), smaller head circumference ( β = −0.41; 95% CI = −0.78, −0.03), and, during the second half of pregnancy, with shorter body length ( β = −0.58; 95% CI = −1.09, −0.07). Furthermore, ETU was nonlinearly associated with head circumference during the second half of pregnancy. Biomarkers of pyrethroids and pyrimethanil were not associated with birth size, and none of the biomarkers explained the length of gestation. Conclusions: Prenatal exposure to chlorpyrifos and 2,4-D, and, possibly, mancozeb/ETU, may impair fetal growth.}, number={2}, journal={ENVIRONMENTAL EPIDEMIOLOGY}, author={Joode, Berna van Wendel and Penaloza-Castaneda, Jorge and Mora, Ana M. and Corrales-Vargas, Andrea and Eskenazi, Brenda and Hoppin, Jane A. and Lindh, Christian H.}, year={2024}, month={Apr} } @article{kotlarz_mccord_wiecha_weed_cuffney_enders_strynar_knappe_reich_hoppin_2024, title={Reanalysis of PFO5DoA Levels in Blood from Wilmington, North Carolina, Residents, 2017-2018}, volume={132}, ISSN={["1552-9924"]}, url={https://doi.org/10.1289/EHP13339}, DOI={10.1289/EHP13339}, abstractNote={,}, number={2}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Wiecha, Nate and Weed, Rebecca A. and Cuffney, Michael and Enders, Jeffrey R. and Strynar, Mark and Knappe, Detlef R. U. and Reich, Brian J. and Hoppin, Jane A.}, year={2024}, month={Feb} } @article{werthmann_joode_cuffney_reich_soto-martinez_corrales-vargas_palomo-cordero_penaloza-castanedac_hoppin_2023, title={A cross-sectional analysis of medical conditions and environmental factors associated with fractional exhaled nitric oxide (FeNO) in women and children from the ISA birth cohort, Costa Rica}, volume={233}, ISSN={["1096-0953"]}, url={https://doi.org/10.1016/j.envres.2023.116449}, DOI={10.1016/j.envres.2023.116449}, abstractNote={Fractional exhaled nitric oxide (FeNO) is a marker of airway inflammation. Elevated FeNO has been associated with environmental exposures, however, studies from tropical countries are limited. Using data from the Infants' Environmental Health Study (ISA) birth cohort, we evaluated medical conditions and environmental exposures' association with elevated FeNO.}, journal={ENVIRONMENTAL RESEARCH}, author={Werthmann, Derek and Joode, Berna van Wendel and Cuffney, Michael T. and Reich, Brian J. and Soto-Martinez, Manuel E. and Corrales-Vargas, Andrea and Palomo-Cordero, Luis and Penaloza-Castanedac, Jorge and Hoppin, Jane A.}, year={2023}, month={Sep} } @article{krais_joode_liljedahl_blomberg_ronnholm_bengtsson_cano_hoppin_littorin_nielsen_et al._2023, title={Detection of the fungicide transformation product 4-hydroxychlorothalonil in serum of pregnant women from Sweden and Costa Rica}, volume={7}, ISSN={["1559-064X"]}, DOI={10.1038/s41370-023-00580-8}, abstractNote={Abstract Background 4-hydroxychlorothalonil (HCT, R182281), a transformation product of the fungicide chlorothalonil, was recently identified in human serum and breast milk. There are indications that HCT may be more toxic and environmentally persistent than chlorothalonil. Objective Our aim was to investigate serum concentrations of HCT in pregnant women in Sweden and Costa Rica. Methods We developed a quantitative analytical method for HCT using liquid chromatography tandem mass spectrometry. We measured HCT in 1808 serum samples from pregnant women from the general population in Sweden (1997–2015) and in 632 samples from 393 pregnant women from an agricultural population in Costa Rica (2010–2011). In Swedish samples, we assessed time trends and investigated seasonality. In the Costa Rican samples, we evaluated variability between and within women and explanatory variables of HCT concentrations. Results HCT was detected in all serum samples, and the limit of detection was 0.1 µg/L. The median HCT concentration in the Swedish samples was 4.1 µg/L (interquartile range [IQR] of 2.9 − 5.8 µg/L), and 3.9 times higher in the Costa Rican samples (median: 16.1 µg/L; IQR: 10.6 − 25.0 µg/L). We found clear seasonal variation with higher concentrations in the first half of each year among Swedish women. In the Costa Rican study, women working in agriculture and living near banana plantations had higher HCT concentrations, whilst higher parity and having a partner working in agriculture were associated with decreased HCT, and no clear seasonal pattern was observed. Impact statement For the first time, this study quantifies human exposure to the fungicide chlorothalonil and/or its transformation product 4-hydroxychlorothalonil (HCT, R182281) and finds higher serum concentrations in women from a tropical agricultural setting as compared with women from the general population in Sweden.}, journal={JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY}, author={Krais, Annette M. M. and Joode, Berna van Wendel and Liljedahl, Emelie Rietz and Blomberg, Annelise J. and Ronnholm, Anna and Bengtsson, Marie and Cano, Juan Camilo and Hoppin, Jane A. A. and Littorin, Margareta and Nielsen, Christel and et al.}, year={2023}, month={Jul} } @article{wallis_kotlarz_knappe_collier_lea_reif_mccord_strynar_dewitt_hoppin_2023, title={Estimation of the Half-Lives of Recently Detected Per- and Polyfluorinated Alkyl Ethers in an Exposed Community}, volume={57}, ISSN={["1520-5851"]}, url={https://doi.org/10.1021/acs.est.2c08241}, DOI={10.1021/acs.est.2c08241}, abstractNote={To estimate half-lives for novel fluoroethers, the GenX Exposure Study obtained two serum measurements for per- and polyfluoroalkyl substances (PFAS) for 44 participants of age 12-86 years from North Carolina, collected 5 and 11 months after fluoroether discharges into the drinking water source were controlled. The estimated half-lives for these compounds were 127 days (95% confidence interval (95% CI) = 86, 243 days) for perfluorotetraoxadecanoic acid (PFO4DA), 296 days for Nafion byproduct 2 (95% CI = 176, 924 days), and 379 days (95% CI = 199, 3870 days) for perfluoro-3,5,7,9,11-pentaoxadodecanoic acid (PFO5DoA). Using these estimates and the literature values, a model was built that predicted PFAS half-lives using structural properties. Three chemical properties predicted 55% of the variance of PFAS half-lives based on 15 PFAS. A model with only molecular weight predicted 69% of the variance. Some properties can predict the half-lives of PFAS, but a deeper understanding is needed. These fluoroethers had biological half-lives longer than published half-lives for PFHxA and PFHpA (30-60 days) but shorter than those for PFOA and PFOS (800-1200 days). These are the first and possibly only estimates of human elimination half-lives of these fluoroethers.}, number={41}, journal={ENVIRONMENTAL SCIENCE & TECHNOLOGY}, author={Wallis, Dylan J. and Kotlarz, Nadine and Knappe, Detlef R. U. and Collier, David N. and Lea, C. Suzanne and Reif, David and McCord, James and Strynar, Mark and DeWitt, Jamie C. and Hoppin, Jane A.}, year={2023}, month={Oct}, pages={15348–15355} } @article{cuffney_wilkie_kotlarz_knappe_lea_collier_dewitt_hoppin_2023, title={Factors associated with per- and polyfluoroalkyl substances (PFAS) serum concentrations in residents of New Hanover County, North Carolina: The GenX exposure study}, volume={237}, ISSN={["1096-0953"]}, url={https://doi.org/10.1016/j.envres.2023.117020}, DOI={10.1016/j.envres.2023.117020}, abstractNote={In 2017, people living in New Hanover County, North Carolina, learned that for ∼40 years they were unknowingly exposed to per- and polyfluoroalkyl substances (PFAS) through drinking water sourced by the Cape Fear River. Using data from the GenX Exposure Study, which measured serum PFAS levels in county residents, we aimed to understand questionnaire-measured factors associated with serum PFAS levels. Because most residents were served by the same municipal water source, we focused on surrogate factors of drinking water exposure that may contribute to variability in PFAS levels. Our analysis included 335 participants aged 6 and older. We included seven chemicals detected in ≥75% of the study population: four well-studied perfluoroalkyl acids (PFOA, PFOS, PFNA, PFHxS) and three understudied fluoroethers (Nafion byproduct 2, PFO4DA, PFO5DoA). For each PFAS, we evaluated associations of variables with serum PFAS levels adjusting for key demographic characteristics. Additionally, we developed predictive models for each PFAS. We used years of residence in the lower Cape Fear Region as a surrogate for water consumption. Duration of drinking water exposure was associated with higher serum levels of all seven PFAS. Drinking municipal water treated by home filters or other sources of water (non-city) were associated with lower PFAS concentrations for all seven PFAS compared to drinking municipal water without additional filtration. Males had higher levels of well-studied PFAS, but there was no difference for fluoroethers. For six PFAS, the predictive models explained ≥30% of the variance in serum PFAS levels. While some factors were significantly associated with levels of individual PFAS, their relative importance to overall prediction was low, such as microwave popcorn consumption. Consistently, water consumption-related variables were important for both the association and predictive investigations. These analyses provide additional evidence that drinking water is a primary source for serum PFAS concentrations among New Hanover County residents.}, journal={ENVIRONMENTAL RESEARCH}, author={Cuffney, Michael and Wilkie, Adrien A. and Kotlarz, Nadine and Knappe, Detlef and Lea, C. Suzanne and Collier, David N. and Dewitt, Jamie and Hoppin, Jane A.}, year={2023}, month={Nov} } @article{hall_zhang_tait_hoffman_collier_hoppin_stapleton_2023, title={PFAS levels in paired drinking water and serum samples collected from an exposed community in Central North Carolina}, volume={895}, ISSN={["1879-1026"]}, DOI={10.1016/j.scitotenv.2023.165091}, abstractNote={The community of Pittsboro, North Carolina has been documented to have extensive per- and polyfluoroalkyl substances (PFAS) contamination in its drinking water source, the Haw River, over the last 20 years. However, a detailed exposure assessment has never been conducted. In this study, we sought to characterize the PFAS in paired drinking water and blood samples collected from a small cohort of Pittsboro residents (n = 49). Drinking water and serum from blood were collected from adults in late 2019 and early 2020 and were analyzed to quantify 13 PFAS analytes. In order to explore potential health effects of PFAS exposure, serum was further analyzed for clinical chemistry endpoints that could be potentially associated with PFAS (e.g., cholesterol, liver function biomarkers). PFAS were detected in all serum samples, and some serum PFAS concentrations were 2 to 4 times higher than the median U.S. serum concentrations reported in the general U.S. population. Of the 13 PFAS in drinking water, perfluorohexanoic acid (PFHxA) was measured at the highest concentrations. PFAS levels in the current drinking water were not associated with current serum PFAS, suggesting that the serum PFAS in this cohort likely reflects historical exposure to PFAS with long half-lives (e.g., PFOS and PFOA). However, one PFAS with a shorter half-life (PFHxA) was observed to increase in serum, reflecting the temporal variability of PFHxA in river and drinking water. Statistical analyses indicated that serum PFOA and PFHxS were positively associated with total cholesterol and non-HDL cholesterol. No serum PFAS was associated with HDL cholesterol. In the clinical chemistry analyses, serum PFHxA was found to be negatively associated with electrolytes and liver enzymes (e.g., AST and ALT), and serum PFOS was found to be positively associated with the ratio of blood urea nitrogen to creatinine (BUN:Cre). While small in size, this study revealed extensive exposure to PFAS in Pittsboro and associations with clinical blood markers, suggesting potential health impacts in community residents.}, journal={SCIENCE OF THE TOTAL ENVIRONMENT}, author={Hall, Samantha M. and Zhang, Sharon and Tait, George H. and Hoffman, Kate and Collier, David N. and Hoppin, Jane A. and Stapleton, Heather M.}, year={2023}, month={Oct} } @article{wallis_barton_knappe_kotlarz_mcdonough_higgins_hoppin_adgate_2023, title={Source apportionment of serum PFASs in two highly exposed communities}, volume={855}, ISSN={["1879-1026"]}, DOI={10.1016/j.scitotenv.2022.158842}, abstractNote={Per- and polyfluoroalkyl substances (PFASs) are synthetic chemicals that are ubiquitous in environmental and biological systems, including human serum. PFASs are used in many products and industrial processes and are tied to numerous health effects. Due to multiple sources and exposure pathways, methods are needed to identify PFAS sources in communities to develop targeted interventions. We assessed effectiveness of three source apportionment methods (UNMIX, positive matrix factorization [PMF], and principal component analysis - multiple linear regression [PCA-MLR]) for identifying contributors to human serum PFAS concentrations in two highly exposed populations in Colorado and North Carolina where drinking water was contaminated via upstream sources, including a Space Force base and a fluorochemical manufacturing plant. UNMIX and PMF models extracted three to four potential PFAS exposure sources in the Colorado and North Carolina cohorts while PCA-MLR classified two in each cohort. No sources were characterized in NHANES (National Health and Nutrition Examination Study). Results suggest that these three methods can successfully identify sources in highly exposed populations. Future PFAS exposure research should focus on analyzing serum for an expanded PFAS panel, identifying cohorts with other distinct point source exposures, and combining biological and environmental data to better understand source apportionment results in the context of PFAS toxicokinetic behavior.}, journal={SCIENCE OF THE TOTAL ENVIRONMENT}, author={Wallis, Dylan J. and Barton, Kelsey E. and Knappe, Detlef R. U. and Kotlarz, Nadine and McDonough, Carrie A. and Higgins, Christopher P. and Hoppin, Jane A. and Adgate, John L.}, year={2023}, month={Jan} } @article{kotlarz_holcomb_pasha_reckling_kays_lai_daly_palani_bailey_guidry_et al._2023, title={Timing and Trends for Municipal Wastewater, Lab-Confirmed Case , and Syndromic Case Surveillance of COVID-19 in Raleigh, North Carolina}, volume={113}, ISSN={["1541-0048"]}, url={https://publons.com/wos-op/publon/54927766/}, DOI={10.2105/AJPH.2022.307108}, abstractNote={To compare 4 COVID-19 surveillance metrics in a major metropolitan area.}, number={1}, journal={AMERICAN JOURNAL OF PUBLIC HEALTH}, publisher={American Public Health Association}, author={Kotlarz, Nadine and Holcomb, David A. and Pasha, Tanvir and Reckling, Stacie and Kays, Judith and Lai, Yi-Chun and Daly, Sean and Palani, Sivaranjani and Bailey, Erika and Guidry, Virginia T. and et al.}, year={2023}, month={Jan}, pages={79–88} } @article{islam_mohamed_umbach_london_henneberger_freeman_sandler_hoppin_2022, title={Allergic and non-allergic wheeze among farm women in the Agricultural Health Study (2005-2010)}, volume={8}, ISSN={["1470-7926"]}, url={https://doi.org/10.1136/oemed-2022-108252}, DOI={10.1136/oemed-2022-108252}, abstractNote={Farms represent complex environments for respiratory exposures including hays, grains and pesticides. Little is known about the impact of these exposures on women's respiratory health. We evaluated the association of farm exposures with allergic and non-allergic wheeze among women in the Agricultural Health Study, a study of farmers and their spouses based in Iowa and North Carolina.}, journal={OCCUPATIONAL AND ENVIRONMENTAL MEDICINE}, author={Islam, Jessica Y. and Mohamed, Ahmed and Umbach, David M. and London, Stephanie J. and Henneberger, Paul K. and Freeman, Laura E. Beane and Sandler, Dale P. and Hoppin, Jane A.}, year={2022}, month={Aug} } @article{rosen_kotlarz_knappe_lea_collier_richardson_hoppin_2022, title={Drinking Water-Associated PFAS and Fluoroethers and Lipid Outcomes in the GenX Exposure Study}, volume={130}, ISSN={["1552-9924"]}, url={https://doi.org/10.1289/EHP11033}, DOI={10.1289/EHP11033}, abstractNote={Background: Residents of Wilmington, North, Carolina, were exposed to drinking water contaminated by fluoroethers and legacy per- and polyfluoroalkyl substances (PFAS), such as perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS), with fluoroether exposure occurring from 1980 to 2017. PFOA and PFOS have previously been associated with metabolic dysfunction; however, few prior studies have examined associations between other PFAS and lipid levels. Objectives: We measured the association between serum fluoroether and legacy PFAS levels and various cholesterol outcomes. Methods: Participants in the GenX Exposure Study contributed nonfasting blood samples in November 2017 and May 2018 that were analyzed for 20 PFAS (10 legacy, 10 fluoroethers) and serum lipids [total cholesterol, low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides] and calculated non-HDL cholesterol. We estimated covariate-adjusted associations between quartiles of exposure to each of the PFAS measures (as well as the summed concentrations of legacy PFAS, fluoroethers, and all 10 targeted PFAS) and lipid outcomes by fitting inverse probability of treatment weighted linear regressions. Results: In this cross-sectional study of 326 participants (age range 6–86 y), eight PFAS were detected in >50% of the population. For PFOS and perfluorononanoic acid (PFNA), non-HDL cholesterol was approximately 5mg/dL higher per exposure quartile increase: [PFOS: 4.89; 95% confidence interval (CI): 0.10, 9.68 and PFNA: 5.25 (95% CI: 0.39, 10.1)], whereas total cholesterol was approximately 6mg/dL higher per quartile [PFOS: 5.71 (95% CI: 0.38, 11.0), PFNA: 5.92 (95% CI: 0.19, 11.7)]. In age-stratified analyses, associations were strongest among the oldest participants. Two fluoroethers were associated with higher HDL, whereas other fluoroether compounds were not associated with serum lipid levels. Discussion: PFNA and PFOS were associated with higher levels of total and non-HDL cholesterol, with associations larger in magnitude among older adults. In the presence of these legacy PFAS, fluoroethers appeared to be associated with HDL but not non-HDL lipid measures. https://doi.org/10.1289/EHP11033}, number={9}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Rosen, Emma M. and Kotlarz, Nadine and Knappe, Detlef R. U. and Lea, C. Suzanne and Collier, David N. and Richardson, David B. and Hoppin, Jane A.}, year={2022}, month={Sep} } @article{vargas_castaneda_liljedahl_mora_menezes-filho_smith_mergler_reich_giffin_hoppin_et al._2022, title={Exposure to common-use pesticides, manganese, lead, and thyroid function among pregnant women from the Infants' Environmental Health (ISA) study, Costa Rica}, volume={810}, ISSN={["1879-1026"]}, DOI={10.1016/j.scitotenv.2021.151288}, abstractNote={Pesticides and metals may disrupt thyroid function, which is key to fetal brain development.}, journal={SCIENCE OF THE TOTAL ENVIRONMENT}, author={Vargas, Andrea Corrales and Castaneda, Jorge Penaloza and Liljedahl, Emelie Rietz and Mora, Ana Maria and Menezes-Filho, Jose Antonio and Smith, Donald R. and Mergler, Donna and Reich, Brian and Giffin, Andrew and Hoppin, Jane A. and et al.}, year={2022}, month={Mar} } @article{giffin_hoppin_cordoba_solano-diaz_ruepert_penaloza-castaneda_lindh_reich_joode_2022, title={Pyrimethanil and chlorpyrifos air concentrations and pregnant women's urinary metabolites in the Infants' Environmental Health Study (ISA) Costa Rica ,}, volume={166}, ISSN={["1873-6750"]}, DOI={10.1016/j.envint.2022.107328}, abstractNote={Only few studies have compared environmental pesticide air concentrations with specific urinary metabolites to evaluate pathways of exposure. Therefore, we compared pyrimethanil and chlorpyrifos concentrations in air with urinary 4-hydroxypyrimethanil (OHP, metabolite of pyrimethanil) and 3,5,6-trichloro-2-pyridinol (TCPy, metabolite of chlorpyrifos) among pregnant women from the Infant's Environmental Health Study (ISA) in Matina County, Costa Rica. During pregnancy, we obtained repeat urinary samples from 448 women enrolled in the ISA study. We extrapolated pyrimethanil and chlorpyrifos concentrations measured with passive air samplers (PAS) (n = 48, from 12 schools), across space and time using a Bayesian spatiotemporal model. We subsequently compared these concentrations with urinary OHP and TCPy in 915 samples from 448 women, using separate mixed models and considering several covariables. A 10% increase in air pyrimethanil (ng/m3) was associated with a 5.7% (95% confidence interval (CI 4.6, 6.8) increase in OHP (μg/L). Women living further from banana plantations had lower OHP: −0.7% (95% CI −1.2, −0.3) for each 10% increase in distance (meters) as well as women who ate rice and beans ≥15 times a week −23% (95% CI −38, −4). In addition, each 1 ng/m3 increase in chlorpyrifos in air was associated with a 1.5% (95% CI 0.2, 2.8) increase in TCPy (μg/L), and women working in agriculture tended to have increased TCPy (21%, 95% CI −2, 49). The Bayesian spatiotemporal models were useful to estimate pyrimethanil and chlorpyrifos air concentrations across space and time. Our results suggest inhalation of pyrimethanil and chlorpyrifos is a pathway of environmental exposure. PAS seems a useful technique to monitor environmental current-use pesticide exposures. For future studies, we recommend increasing the number of locations of environmental air measurements, obtaining all air and urine measurements during the same month, and, ideally, including dermal exposure estimates as well.}, journal={ENVIRONMENT INTERNATIONAL}, author={Giffin, Andrew and Hoppin, Jane A. and Cordoba, Leonel and Solano-Diaz, Karla and Ruepert, Clemens and Penaloza-Castaneda, Jorge and Lindh, Christian and Reich, Brian J. and Joode, Berna van Wendel}, year={2022}, month={Aug} } @article{islam_hoppin_mora_soto-martinez_cordoba gamboa_penaloza castaneda_reich_lindh_joode_2022, title={Respiratory and allergic outcomes among 5-year-old children exposed to pesticides}, volume={2}, ISSN={["1468-3296"]}, DOI={10.1136/thoraxjnl-2021-218068}, abstractNote={Background Little is known about the effects of pesticides on children’s respiratory and allergic outcomes. We evaluated associations of prenatal and current pesticide exposures with respiratory and allergic outcomes in children from the Infants’ Environmental Health Study in Costa Rica. Methods Among 5-year-old children (n=303), we measured prenatal and current specific gravity-corrected urinary metabolite concentrations of insecticides (chlorpyrifos, pyrethroids), fungicides (mancozeb, pyrimethanil, thiabendazole) and 2,4-D. We collected information from caregivers on respiratory (ever doctor-diagnosed asthma and lower respiratory tract infections (LRTI), wheeze and cough during last 12 months) and allergic (nasal allergies, itchy rash, ever eczema) outcomes. We fitted separate multivariable logistic regression models for high (≥75th percentile (P75)) vs low (128,000 individuals; 44% of participants were female. Farming practices varied from subsistence farming to large-scale industrial agriculture. All cohorts provided respiratory outcome information for their cohort based on their study definitions. The majority of outcomes were based on self-report using standard respiratory questionnaires; the greatest variability in assessment methods was associated with chronic obstructive pulmonary disease (COPD).Results: For all three respiratory symptoms (cough, phlegm, and wheeze), the median prevalence in men was higher than in women, with the greatest difference for phlegm (17% vs. 10%). For asthma, women had a higher prevalence (7.8% vs 6.5%), with the difference associated with allergic asthma. The relative proportion of allergic asthma varied among cohorts. In two of eight cohorts for women and two of seven cohorts for men, allergic asthma was more common than non-allergic asthma.Conclusions: These findings indicate that respiratory outcomes are common among farmers around the world despite differences in agricultural production. As women in the general population are at higher risk of asthma, exploring gender differences in occupational studies is critical for a deeper understanding of respiratory disease among agricultural workers.}, number={2}, journal={JOURNAL OF AGROMEDICINE}, author={Fix, Jonathan and Annesi-Maesano, Isabella and Baldi, Isabelle and Boulanger, Mathilde and Cheng, Soo and Cortes, Sandra and Dalphin, Jean-Charles and Dalvie, Mohamed Aqiel and Degano, Bruno and Douwes, Jeroen and et al.}, year={2021}, month={Apr}, pages={97–108} } @article{kamai_villanger_nethery_thomsen_sakhi_drover_hoppin_knudsen_reichborn-kjennerud_zeiner_et al._2021, title={Gestational Phthalate Exposure and Preschool Attention Deficit Hyperactivity Disorder in Norway}, volume={5}, ISSN={["2474-7882"]}, DOI={10.1097/EE9.0000000000000161}, abstractNote={Prenatal phthalate exposure has been linked to altered neurobehavioral development in both animal models and epidemiologic studies, but whether or not these associations translate to increased risk of neurodevelopmental disorders is unclear. We used a nested case-cohort study design to assess whether maternal urinary concentrations of 12 phthalate metabolites at 17 weeks gestation were associated with criteria for Attention Deficit Hyperactivity Disorder (ADHD) classified among 3-year-old children in the Norwegian Mother, Father and Child Cohort Study (MoBa). Between 2007 and 2011, 260 children in this substudy were classified with ADHD using a standardized, on-site clinical assessment; they were compared with 549 population-based controls. We modeled phthalate levels both linearly and by quintiles in logistic regression models adjusted for relevant covariates and tested for interaction by child sex. Children of mothers in the highest quintile of di-iso-nonyl phthalate (∑DiNP) metabolite levels had 1.70 times the odds of being classified with ADHD compared with those in the lowest quintile (95% confidence interval [CI] = 1.03 to 2.82). In linear models, there was a trend with the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP); each natural log-unit increase in concentration was associated with 1.22 times the odds of ADHD (95% CI = 0.99 to 1.52). In boys, but not girls, mono-n-butyl phthalate exposure was associated with increased odds of ADHD (odds ratio [OR] 1.42; 95% CI = 1.07 to 1.88). Additional adjustment for correlated phthalate metabolites attenuated estimates. These results suggest gestational phthalate exposure may impact the behavior of children as young as 3 years.}, number={4}, journal={ENVIRONMENTAL EPIDEMIOLOGY}, author={Kamai, Elizabeth M. and Villanger, Gro D. and Nethery, Rachel C. and Thomsen, Cathrine and Sakhi, Amrit K. and Drover, Samantha S. M. and Hoppin, Jane A. and Knudsen, Gun Peggy and Reichborn-Kjennerud, Ted and Zeiner, Pal and et al.}, year={2021}, month={Aug} } @article{villanger_drover_nethery_thomsen_sakhi_overgaard_zeiner_hoppin_reichborn-kjennerud_aase_et al._2020, title={Associations between urine phthalate metabolites and thyroid function in pregnant women and the influence of iodine status}, volume={137}, ISSN={["1873-6750"]}, DOI={10.1016/j.envint.2020.105509}, abstractNote={Human populations, including susceptible subpopulations such as pregnant women and their fetuses, are continuously exposed to phthalates. Phthalates may affect the thyroid hormone system, causing concern for pregnancy health, birth outcomes and child development. Few studies have investigated the joint effect of phthalates on thyroid function in pregnant women, although they are present as a mixture with highly inter-correlated compounds. Additionally, no studies have investigated if the key nutrient for thyroid health, iodine, modifies these relationships. In this study, we examined the cross-sectional relationships between concentrations of 12 urinary phthalate metabolites and 6 plasma thyroid function biomarkers measured mid-pregnancy (~17 week gestation) in pregnant women (N = 1072), that were selected from a population-based prospective birth cohort, The Norwegian Mother, Father and Child Cohort study (MoBa). We investigated if the phthalate metabolite-thyroid function biomarker associations differed by iodine status by using a validated estimate of habitual dietary iodine intake based on a food frequency questionnaire from the 22nd gestation week. We accounted for the phthalate metabolite mixture by factor analyses, ultimately reducing the exposure into two uncorrelated factors. These factors were used as predictors in multivariable adjusted linear regression models with thyroid function biomarkers as the outcomes. Factor 1, which included high loadings for mono-iso-butyl phthalate (MiBP), mono-n-butyl phthalate (MnBP), and monobenzyl phthalate (MBzP), was associated with increased total triiodothyronine (TT3) and free T3 index (fT3i). These associations appeared to be driven primarily by women with low iodine intake (<150 µg/day, ~70% of our sample). Iodine intake significantly modified (p-interaction < 0.05) the association of factor 1 with thyroid stimulating hormone (TSH), total thyroxine (TT4) and free T4 index (fT4i), such that only among women in the high iodine intake category (≥150 µg/day, i.e. sufficient) was this factor associated with increased TSH and decreased TT4 and FT4i, respectively. In contrast, factor 2, which included high loadings for di-2-ethylhexyl phthalate metabolites (∑DEHP) and di-iso-nonyl phthalate metabolites (∑DiNP), was associated with a decrease in TT3 and fT3i, which appeared fairly uniform across iodine intake categories. We find that phthalate exposure is associated with thyroid function in mid-pregnancy among Norwegian women, and that iodine intake, which is essential for thyroid health, could influence some of these relationships.}, journal={ENVIRONMENT INTERNATIONAL}, author={Villanger, Gro D. and Drover, Samantha S. M. and Nethery, Rachel C. and Thomsen, Cathrine and Sakhi, Amrit K. and Overgaard, Kristin R. and Zeiner, Pal and Hoppin, Jane A. and Reichborn-Kjennerud, Ted and Aase, Heidi and et al.}, year={2020}, month={Apr} } @article{kotlarz_mccord_collier_lea_strynar_lindstrom_wilkie_islam_matney_tarte_et al._2020, title={Measurement of Novel, Drinking Water-Associated PFAS in Blood from Adults and Children in Wilmington, North Carolina}, volume={128}, ISSN={["1552-9924"]}, DOI={10.1289/EHP6837}, abstractNote={From 1980 to 2017, a fluorochemical manufacturing facility discharged wastewater containing poorly understood per- and polyfluoroalkyl substances (PFAS) to the Cape Fear River, the primary drinking water source for Wilmington, North Carolina, residents. Those PFAS included several fluoroethers including HFPO-DA also known as GenX. Little is known about the bioaccumulation potential of these fluoroethers.}, number={7}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Kotlarz, Nadine and McCord, James and Collier, David and Lea, C. Suzanne and Strynar, Mark and Lindstrom, Andrew B. and Wilkie, Adrien A. and Islam, Jessica Y. and Matney, Katelyn and Tarte, Phillip and et al.}, year={2020}, month={Jul} } @article{mora_hoppin_cordoba_cano_soto-martinez_eskenazi_lindh_joode_2020, title={Prenatal pesticide exposure and respiratory health outcomes in the first year of life: Results from the infants' Environmental Health (ISA) study}, volume={225}, ISSN={["1618-131X"]}, DOI={10.1016/j.ijheh.2020.113474}, abstractNote={Growing evidence suggests that pesticide exposure may influence respiratory health, but data in young children are very limited. We examined the association of prenatal pesticide exposure with lower respiratory tract infections (LRTIs) and wheeze at one year of age in children from the Infants' Environmental Health (ISA) study in Costa Rica.We measured seven pesticide metabolites, including ethylenethiourea (ETU, metabolite of mancozeb), in maternal urine samples collected repeatedly during pregnancy. For each woman, we averaged pesticide concentrations during each half of pregnancy (≤20 and >20 weeks of gestation) and across repeated samples collected over the course of pregnancy. We collected information about LRTIs (n = 355) and wheezing (n = 272) during the first year of life from mothers when their children were 11-19 months old. We fit multivariable logistic regression models using high (quartile 4) vs. low (quartiles 1-3) urinary pesticide concentrations as exposures and adjusted models for maternal age, education, parity, gestational age at birth, and child sex.Ten percent of the children had at least one LRTI and 39% had at least one episode of wheezing during their first year of life. Median (25-75th percentile) specific gravity-corrected urinary ETU concentrations during the first half, second half, and over the course of pregnancy were 3.4 (2.1-5.0), 3.3 (2.2-4.7), and 3.4 (2.4-5.0) ng/mL, respectively. We observed that high urinary ETU concentrations during the first half of pregnancy were associated with increased odds of LRTI (OR = 2.45; 95% CI: 0.96, 6.26), whereas high urinary ETU concentrations during the second half of pregnancy were associated with decreased odds of wheezing (OR = 0.50; 95% CI: 0.26, 0.96). We found that the association between high urinary ETU concentrations during the first half of pregnancy and LRTIs persisted among mother-child pairs with either high or low ETU concentrations during the second half. In contrast, the association of high urinary ETU concentrations during the second half of pregnancy with wheezing was attenuated when we simultaneously adjusted for urinary ETU concentrations during the first half. We observed null associations between other pesticide metabolites measured during pregnancy and respiratory outcomes.Our data indicate that exposure to mancozeb/ETU during the first half of pregnancy may be associated with respiratory outcomes in the first year of life.}, journal={INTERNATIONAL JOURNAL OF HYGIENE AND ENVIRONMENTAL HEALTH}, author={Mora, Ana M. and Hoppin, Jane A. and Cordoba, Leonel and Cano, Juan C. and Soto-Martinez, Manuel and Eskenazi, Brenda and Lindh, Christian H. and Joode, Berna}, year={2020}, month={Apr} } @article{wei_reich_hoppin_ghosal_2020, title={SPARSE BAYESIAN ADDITIVE NONPARAMETRIC REGRESSION WITH APPLICATION TO HEALTH EFFECTS OF PESTICIDES MIXTURES}, volume={30}, ISSN={["1996-8507"]}, DOI={10.5705/ss.202017.0315}, abstractNote={In many practical problems that simultaneously investigate the joint effect of covariates, we first need to identify the subset of significant covariates, and then estimate their joint effect. An example is an epidemiological study that analyzes the effects of exposure variables on a health response. In order to make inferences on the covariate effects, we propose a Bayesian additive nonparametric regression model with a multivariate continuous shrinkage prior to address the model uncertainty and to identify important covariates. Our general approach is to decompose the response function into the sum of the nonlinear main effects and the two-way interaction terms. Then we apply the computationally advantageous Bayesian variable selection method to identify the important effects. The proposed Bayesian method is a multivariate Dirichlet–Laplace prior that aggressively shrinks many terms toward zero, thus mitigating the noise of including unimportant exposures and isolating the effects of the important covariates. Our theoretical studies demonstrate asymptotic prediction and variable selection consistency properties. In addition, we use numerical simulations to evaluate the model performance in terms of prediction and variable selection under practical scenarios. The method is applied to a neurobehavioral data set from the Agricultural Health Study that investigates the association between pesticide usage and neurobehavioral outcomes in farmers. The proposed method shows improved accuracy in predicting the joint effects on the neurobehavioral responses, while restricting the number of covariates included in the model through variable selection.}, number={1}, journal={STATISTICA SINICA}, author={Wei, Ran and Reich, Brian J. and Hoppin, Jane A. and Ghosal, Subhashis}, year={2020}, month={Jan}, pages={55–79} } @article{deziel_freeman_hoppin_thomas_lerro_jones_hines_blair_graubard_lubin_et al._2019, title={An algorithm for quantitatively estimating non-occupational pesticide exposure intensity for spouses in the Agricultural Health Study}, volume={29}, ISSN={["1559-064X"]}, DOI={10.1038/s41370-018-0088-z}, abstractNote={Residents of agricultural areas experience pesticide exposures from sources other than direct agricultural work. We developed a quantitative, active ingredient-specific algorithm for cumulative (adult, married lifetime) non-occupational pesticide exposure intensity for spouses of farmers who applied pesticides in the Agricultural Health Study (AHS). The algorithm addressed three exposure pathways: take-home, agricultural drift, and residential pesticide use. Pathway-specific equations combined (i) weights derived from previous meta-analyses of published pesticide exposure data and (ii) information from the questionnaire on frequency and duration of pesticide use by applicators, home proximity to treated fields, residential pesticide usage (e.g., termite treatments), and spouse’s off-farm employment (proxy for time at home). The residential use equation also incorporated a published probability matrix that documented the likelihood active ingredients were used in home pest treatment products. We illustrate use of these equations by calculating exposure intensities for the insecticide chlorpyrifos and herbicide atrazine for 19,959 spouses. Non-zero estimates for ≥1 pathway were found for 78% and 77% of spouses for chlorpyrifos and atrazine, respectively. Variability in exposed spouses’ intensity estimates was observed for both pesticides, with 75th to 25th percentile ratios ranging from 7.1 to 7.3 for take-home, 6.5 to 8.5 for drift, 2.4 to 2.8 for residential use, and 3.8 to 7.0 for the summed pathways. Take-home and drift estimates were highly correlated (≥0.98), but were not correlated with residential use (0.01‒0.02). This algorithm represents an important advancement in quantifying non-occupational pesticide relative exposure differences and will facilitate improved etiologic analyses in the AHS spouses. The algorithm could be adapted to studies with similar information.}, number={3}, journal={JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY}, author={Deziel, Nicole C. and Freeman, Laura E. Beane and Hoppin, Jane A. and Thomas, Kent and Lerro, Catherine C. and Jones, Rena R. and Hines, Cynthia J. and Blair, Aaron and Graubard, Barry I and Lubin, Jay H. and et al.}, year={2019}, month={Apr}, pages={344–357} } @article{rinsky_richardson_kreiss_nylander-french_freeman_london_henneberger_hoppin_2019, title={Animal production, insecticide use and self-reported symptoms and diagnoses of COPD, including chronic bronchitis, in the Agricultural Health Study}, volume={127}, ISSN={["1873-6750"]}, DOI={10.1016/j.envint.2019.02.049}, abstractNote={Occupational exposure to animal production is associated with chronic bronchitis symptoms; however, few studies consider associations with chronic obstructive pulmonary disease (COPD). We estimated associations between animal production activities and prevalence of self-reported COPD among farmers in the Agricultural Health Study.During a 2005-2010 interview, farmers self-reported information about: their operations (i.e., size, type, number of animals, insecticide use), respiratory symptoms, and COPD diagnoses (i.e., COPD, chronic bronchitis, emphysema). Operations were classified as small or medium/large based on regulatory definitions. Farmers were classified as having a COPD diagnosis, chronic bronchitis symptoms (cough and phlegm for ≥3 months during 2 consecutive years), or both. Polytomous logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI).Of 22,491 participating farmers (median age: 59 years), 922 (4%) reported a COPD diagnosis only, 254 (1%) reported a diagnosis and symptoms, and 962 (4%) reported symptoms only. Compared to raising no commercial animals, raising animals on a medium/large operation was positively associated with chronic bronchitis symptoms with (OR: 1.59; 95% CI: 1.16, 2.18) and without a diagnosis (OR: 1.69; 95% CI: 1.42, 2.01). Ever use of multiple organophosphates, carbaryl, lindane, and permethrin were positively associated with chronic bronchitis symptoms.Animal production work, including insecticide use, was positively associated with chronic bronchitis symptoms; but not consistently with COPD diagnosis alone. Our results support the need for further investigation into the role of animal production-related exposures in the etiology of COPD and better respiratory protection for agricultural workers.}, journal={ENVIRONMENT INTERNATIONAL}, author={Rinsky, Jessica L. and Richardson, David B. and Kreiss, Kathleen and Nylander-French, Leena and Freeman, Laura E. Beane and London, Stephanie J. and Henneberger, Paul K. and Hoppin, Jane A.}, year={2019}, month={Jun}, pages={764–772} } @article{kosnik_reif_lobdell_astell-burt_feng_hader_hoppin_2019, title={Associations between access to healthcare, environmental quality, and end-stage renal disease survival time: Proportional-hazards models of over 1,000,000 people over 14 years}, volume={14}, ISSN={["1932-6203"]}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-85063354945&partnerID=MN8TOARS}, DOI={10.1371/journal.pone.0214094}, abstractNote={Prevalence of end-stage renal disease (ESRD) in the US increased by 74% from 2000 to 2013. To investigate the role of the broader environment on ESRD survival time, we evaluated average distance to the nearest hospital by county (as a surrogate for access to healthcare) and the Environmental Quality Index (EQI), an aggregate measure of ambient environmental quality composed of five domains (air, water, land, built, and sociodemographic), at the county level across the US. Associations between average hospital distance, EQI, and survival time for 1,092,281 people diagnosed with ESRD between 2000 and 2013 (age 18+, without changes in county residence) from the US Renal Data System were evaluated using proportional-hazards models adjusting for gender, race, age at first ESRD service date, BMI, alcohol and tobacco use, and rurality. The models compared the average distance to the nearest hospital (<10, 10–20, >20 miles) and overall EQI percentiles [0–5), [5–20), [20–40), [40–60), [60–80), [80–95), and [95–100], where lower percentiles are interpreted as better EQI. In the full, non-stratified model with both distance and EQI, there was increased survival for patients over 20 miles from a hospital compared to those under 10 miles from a hospital (hazard ratio = 1.14, 95% confidence interval = 1.12–1.15) and no consistent direction of association across EQI strata. In the full model stratified by average hospital distance, under 10 miles from a hospital had increased survival in the worst EQI strata (median survival 3.0 vs. 3.5 years for best vs. worst EQI, respectively), however for people over 20 miles from a hospital, median survival was higher in the best (4.2 years) vs worst (3.4 years) EQI. This association held across different rural/urban categories and age groups. These results demonstrate the importance of considering multiple factors when studying ESRD survival and future efforts should consider additional components of the broader environment.}, number={3}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Kosnik, Marissa B. and Reif, David M. and Lobdell, Danelle T. and Astell-Burt, Thomas and Feng, Xiaoqi and Hader, John D. and Hoppin, Jane A.}, editor={Cheungpasitporn, WisitEditor}, year={2019}, month={Mar} } @article{strassle_smit_hoppin_2018, title={Endotoxin enhances respiratory effects of phthalates in adults: Results from NHANES 2005-6}, volume={162}, ISSN={["1096-0953"]}, DOI={10.1016/j.envres.2018.01.017}, abstractNote={Phthalates have been associated with respiratory symptoms in adults; they may enhance effects of inflammatory compounds. To assess the potential interactions of phthalates and endotoxin on respiratory and allergic symptoms in adults, we used cross-sectional information from the 1091 adults with complete data on urinary phthalates and house dust endotoxin from NHANES 2005–2006. We used multivariable logistic regression to assess whether endotoxin levels modified the association between nine phthalate metabolites and four current allergic symptoms (asthma, wheeze, hay fever, and rhinitis). Endotoxin was classified into tertiles (<10, 10–25, >25 EU/mg dust). Urinary phthalate and dust endotoxin levels were not correlated (r < |0.02|). Under low endotoxin conditions, no associations between phthalates and respiratory outcomes were observed. Under medium or high endotoxin conditions, exposure-response relationships were observed between specific phthalates and wheeze and asthma. For wheeze, three phthalates (mono-benzyl phthalate (MBzP), mono(carboxyoctyl) phthalate (MCOP), and di-ethylhexyl phthalate (DEHP) had significant interactions with endotoxin); for asthma, two phthalates (MCOP and mono(carboxyoctyl) phthalate (MCNP)) had significant interactions. Endotoxin did not modify the associations between phthalates and hay fever or rhinitis. These results are consistent with the hypothesis that endotoxin enhances the respiratory toxicity of phthalates; however this cross-sectional study cannot address key temporal issues. The lack of an association between wheeze or asthma and phthalates when endotoxin exposure was low suggests that phthalates alone may not increase these symptoms.}, journal={ENVIRONMENTAL RESEARCH}, author={Strassle, Paula D. and Smit, Lidwien A. M. and Hoppin, Jane A.}, year={2018}, month={Apr}, pages={280–286} } @article{engel_villanger_nethery_thomsen_sakhi_drover_hoppin_zeiner_knudsen_reichborn-kjennerud_et al._2018, title={Prenatal Phthalates, Maternal Thyroid Function, and Risk of Attention-Deficit Hyperactivity Disorder in the Norwegian Mother and Child Cohort}, volume={126}, ISSN={["1552-9924"]}, DOI={10.1289/ehp2358}, abstractNote={There is growing concern that phthalate exposures may have an impact on child neurodevelopment. Prenatal exposure to phthalates has been linked with externalizing behaviors and executive functioning defects suggestive of an attention-deficit hyperactivity disorder (ADHD) phenotype.We undertook an investigation into whether prenatal exposure to phthalates was associated with clinically confirmed ADHD in a population-based nested case-control study of the Norwegian Mother and Child Cohort (MoBa) between the years 2003 and 2008.Phthalate metabolites were measured in maternal urine collected at midpregnancy. Cases of ADHD (n=297) were obtained through linkage between MoBa and the Norwegian National Patient Registry. A random sample of controls (n=553) from the MoBa population was obtained.In multivariable adjusted coexposure models, the sum of di-2-ethylhexyl phthalate metabolites (∑DEHP) was associated with a monotonically increasing risk of ADHD. Children of mothers in the highest quintile of ∑DEHP had almost three times the odds of an ADHD diagnosis as those in the lowest [OR=2.99 (95% CI: 1.47, 5.49)]. When ∑DEHP was modeled as a log-linear (natural log) term, for each log-unit increase in exposure, the odds of ADHD increased by 47% [OR=1.47 (95% CI: 1.09, 1.94)]. We detected no significant modification by sex or mediation by prenatal maternal thyroid function or by preterm delivery.In this population-based case-control study of clinical ADHD, maternal urinary concentrations of DEHP were monotonically associated with increased risk of ADHD. Additional research is needed to evaluate potential mechanisms linking phthalates to ADHD. https://doi.org/10.1289/EHP2358.}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Engel, Stephanie M. and Villanger, Gro D. and Nethery, Rachel C. and Thomsen, Cathrine and Sakhi, Amrit K. and Drover, Samantha S. M. and Hoppin, Jane A. and Zeiner, Pal and Knudsen, Gun Peggy and Reichborn-Kjennerud, Ted and et al.}, year={2018}, month={May} } @article{baumert_carnes_hoppin_jackson_sandler_freeman_henneberger_umbach_shrestha_long_et al._2018, title={Sleep apnea and pesticide exposure in a study of US farmers}, volume={4}, ISSN={["2352-7226"]}, DOI={10.1016/j.sleh.2017.08.006}, abstractNote={Carbamate and organophosphate pesticides inhibit acetylcholinesterase, and poisoning leads to respiratory depression. Thus, involvement in sleep apnea is plausible, but no data exist at lower levels of exposure. Other pesticides could impact sleep apnea by different mechanisms but have not been studied. Our study examines the associations between pesticide exposure and sleep apnea among pesticide applicators from a US farming population. We analyzed data from 1569 male pesticide applicators, mostly farmers, from an asthma case-control study nested within the prospective Agricultural Health Study. On questionnaires, participants reported use of specific pesticides and physician diagnosis plus prescribed treatments for sleep apnea. We used multivariable logistic regression to estimate associations between ever use of 63 pesticides and sleep apnea (234 cases, 1335 noncases). The most notable association was for carbofuran, a carbamate (100 exposed cases, odds ratio 1.83, 95% confidence interval 1.34-2.51, P = .0002). Carbofuran use began before reported onset of sleep apnea in all cases. This study adds to the known adverse health outcomes of exposure to carbofuran, a pesticide canceled in the United States in 2009 for most agricultural purposes but persists in the environment and remains in use in some other countries. We conducted the first epidemiological study investigating the association of pesticide exposure and sleep apnea. Our results in a male agricultural population suggests that exposure to carbofuran is positively associated with sleep apnea.}, number={1}, journal={SLEEP HEALTH}, author={Baumert, Brittney O. and Carnes, Megan Ulmer and Hoppin, Jane A. and Jackson, Chandra L. and Sandler, Dale P. and Freeman, Laura Beane and Henneberger, Paul K. and Umbach, David M. and Shrestha, Srishti and Long, Stuart and et al.}, year={2018}, month={Feb}, pages={20–26} } @article{turner_nieuwenhuijsen_anderson_balshaw_cui_dunton_hoppin_koutrakis_jerrett_2017, title={Assessing the Exposome with External Measures: Commentary on the State of the Science and Research Recommendations}, volume={38}, ISSN={0163-7525 1545-2093}, url={http://dx.doi.org/10.1146/annurev-publhealth-082516-012802}, DOI={10.1146/annurev-publhealth-082516-012802}, abstractNote={The exposome comprises all environmental exposures that a person experiences from conception throughout the life course. Here we review the state of the science for assessing external exposures within the exposome. This article reviews (a) categories of exposures that can be assessed externally, (b) the current state of the science in external exposure assessment, (c) current tools available for external exposure assessment, and (d) priority research needs. We describe major scientific and technological advances that inform external assessment of the exposome, including geographic information systems; remote sensing; global positioning system and geolocation technologies; portable and personal sensing, including smartphone-based sensors and assessments; and self-reported questionnaire assessments, which increasingly rely on Internet-based platforms. We also discuss priority research needs related to methodological and technological improvement, data analysis and interpretation, data sharing, and other practical considerations, including improved assessment of exposure variability as well as exposure in multiple, critical life stages.}, number={1}, journal={Annual Review of Public Health}, publisher={Annual Reviews}, author={Turner, Michelle C. and Nieuwenhuijsen, Mark and Anderson, Kim and Balshaw, David and Cui, Yuxia and Dunton, Genevieve and Hoppin, Jane A. and Koutrakis, Petros and Jerrett, Michael}, year={2017}, month={Mar}, pages={215–239} } @article{rinsky_richardson_wing_beard_alavanja_beane freeman_chen_henneberger_kamel_sandler_et al._2017, title={Assessing the Potential for Bias From Nonresponse to a Study Follow-up Interview: An Example From the Agricultural Health Study}, volume={186}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwx098}, DOI={10.1093/aje/kwx098}, abstractNote={Prospective cohort studies are important tools for identifying causes of disease. However, these studies are susceptible to attrition. When information collected after enrollment is through interview or exam, attrition leads to missing information for nonrespondents. The Agricultural Health Study enrolled 52,394 farmers in 1993–1997 and collected additional information during subsequent interviews. Forty-six percent of enrolled farmers responded to the 2005–2010 interview; 7% of farmers died prior to the interview. We examined whether response was related to attributes measured at enrollment. To characterize potential bias from attrition, we evaluated differences in associations between smoking and incidence of 3 cancer types between the enrolled cohort and the subcohort of 2005–2010 respondents, using cancer registry information. In the subcohort we evaluated the ability of inverse probability weighting (IPW) to reduce bias. Response was related to age, state, race/ethnicity, education, marital status, smoking, and alcohol consumption. When exposure and outcome were associated and case response was differential by exposure, some bias was observed; IPW conditional on exposure and covariates failed to correct estimates. When response was nondifferential, subcohort and full-cohort estimates were similar, making IPW unnecessary. This example provides a demonstration of investigating the influence of attrition in cohort studies using information that has been self-reported after enrollment.}, number={4}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Rinsky, Jessica L. and Richardson, David B. and Wing, Steve and Beard, John D. and Alavanja, Michael and Beane Freeman, Laura E. and Chen, Honglei and Henneberger, Paul K. and Kamel, Freya and Sandler, Dale P. and et al.}, year={2017}, month={Jul}, pages={395–404} } @article{house_wyss_hoppin_richards_long_umbach_henneberger_freeman_le_dp_et al._2017, title={Early-life farm exposures and adult asthma and atopy in the Agricultural Lung Health Study}, volume={140}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2016.09.036}, DOI={10.1016/j.jaci.2016.09.036}, abstractNote={BackgroundPrevious studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults.ObjectiveWe sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population.MethodsWe analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study. Current asthma and early-life farming exposures were assessed via questionnaires. We defined atopy based on specific IgE > 0.70 IU/mL to at least 1 of 10 allergens measured in blood. We used logistic regression, adjusted for age, sex, race, state (Iowa or North Carolina), and smoking (pack years), to estimate associations between early-life exposures and asthma (1198 cases and 2031 noncases) or atopy (578 cases and 2526 noncases).ResultsExposure to the farming environment in utero and in early childhood had little or no association with asthma but was associated with reduced odds of atopy. The strongest association was seen for having a mother who performed farm activities while pregnant (odds ratio, 0.60; 95% CI, 0.48-0.74) and remained significant in models with correlated early-life exposures including early childhood farm animal contact and raw milk consumption.ConclusionsIn a large US farming population, early-life farm exposures, particularly maternal farming activities while pregnant, were strongly associated with reduced risk of atopy in adults. These results extend previous work done primarily on childhood outcomes and suggest that protective associations of early-life farming exposures on atopy endure across the life course. Previous studies, mostly from Europe, suggest that early-life farming exposures protect against childhood asthma and allergy; few data exist on asthma and allergy in adults. We sought to examine associations between early-life farming exposures and current asthma and atopy in an older adult US farming population. We analyzed data from 1746 farmers and 1555 spouses (mean age, 63) from a case-control study nested within the Agricultural Health Study. Current asthma and early-life farming exposures were assessed via questionnaires. We defined atopy based on specific IgE > 0.70 IU/mL to at least 1 of 10 allergens measured in blood. We used logistic regression, adjusted for age, sex, race, state (Iowa or North Carolina), and smoking (pack years), to estimate associations between early-life exposures and asthma (1198 cases and 2031 noncases) or atopy (578 cases and 2526 noncases). Exposure to the farming environment in utero and in early childhood had little or no association with asthma but was associated with reduced odds of atopy. The strongest association was seen for having a mother who performed farm activities while pregnant (odds ratio, 0.60; 95% CI, 0.48-0.74) and remained significant in models with correlated early-life exposures including early childhood farm animal contact and raw milk consumption. In a large US farming population, early-life farm exposures, particularly maternal farming activities while pregnant, were strongly associated with reduced risk of atopy in adults. These results extend previous work done primarily on childhood outcomes and suggest that protective associations of early-life farming exposures on atopy endure across the life course.}, number={1}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={House, J.S. and Wyss, A.B. and Hoppin, J.A. and Richards, M. and Long, S. and Umbach, D.M. and Henneberger, P.K. and Freeman, Beane and Le, Sandler and Dp, Long O.'Connell and et al.}, year={2017}, month={Jul}, pages={249–256.e14} } @article{carnes_hoppin_metwali_wyss_hankinson_o’connell_richards_long_freeman_sandler_et al._2017, title={House Dust Endotoxin Levels Are Associated with Adult Asthma in a U.S. Farming Population}, volume={14}, ISSN={2329-6933 2325-6621}, url={http://dx.doi.org/10.1513/AnnalsATS.201611-861OC}, DOI={10.1513/annalsats.201611-861oc}, abstractNote={Endotoxin initiates a proinflammatory response from the innate immune system. Studies in children suggest that endotoxin exposure from house dust may be an important risk factor for asthma, but few studies have been conducted in adult populations.To investigate the association of house dust endotoxin levels with asthma and related phenotypes (wheeze, atopy, and pulmonary function) in a large U.S. farming population.Dust was collected from the bedrooms (n = 2,485) of participants enrolled in a case-control study of current asthma (927 cases) nested within the Agricultural Health Study. Dust endotoxin was measured by Limulus amebocyte lysate assay. Outcomes were measured by questionnaire, spirometry, and blood draw. We evaluated associations using linear and logistic regression.Endotoxin was significantly associated with current asthma (odds ratio [OR], 1.30; 95% confidence interval [CI], 1.14-1.47), and this relationship was modified by early-life farm exposure (born on a farm: OR, 1.18; 95% CI, 1.02-1.37; not born on a farm: OR, 1.67; 95% CI, 1.26-2.20; Interaction P = 0.05). Significant positive associations were seen with both atopic and nonatopic asthma. Endotoxin was not related to either atopy or wheeze. Higher endotoxin was related to lower FEV1/FVC in asthma cases only (Interaction P = 0.01). For asthma, there was suggestive evidence of a gene-by-environment interaction for the CD14 variant rs2569190 (Interaction P = 0.16) but not for the TLR4 variants rs4986790 and rs4986791.House dust endotoxin was associated with current atopic and nonatopic asthma in a U.S. farming population. The degree of the association with asthma depended on early-life farm exposures. Furthermore, endotoxin was associated with lower pulmonary function in patients with asthma.}, number={3}, journal={Annals of the American Thoracic Society}, publisher={American Thoracic Society}, author={Carnes, Megan Ulmer and Hoppin, Jane A. and Metwali, Nervana and Wyss, Annah B. and Hankinson, John L. and O’Connell, Elizabeth Long and Richards, Marie and Long, Stuart and Freeman, Laura E. Beane and Sandler, Dale P. and et al.}, year={2017}, month={Mar}, pages={324–331} } @article{fessler_carnes_salo_wilkerson_cohn_king_hoppin_sandler_travlos_london_et al._2017, title={House Dust Endotoxin and Periphera lLeukocyte Counts: Results from Two Large Epidemiologic Studies}, volume={125}, ISSN={["1552-9924"]}, DOI={10.1289/ehp661}, abstractNote={The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood.We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects.The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term.There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×103/μL (95% CI: 0.070, 0.301×103/μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15).This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661.}, number={5}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Fessler, Michael B. and Carnes, Megan U. and Salo, Paivi M. and Wilkerson, Jesse and Cohn, Richard D. and King, Debra and Hoppin, Jane A. and Sandler, Dale P. and Travlos, Greg and London, Stephanie J. and et al.}, year={2017}, month={May} } @article{engel_werder_satagopan_blair_hoppin_koutros_lerro_sandler_alavanja_freeman_et al._2017, title={Insecticide Use and Breast Cancer Riskamong Farmers' Wives in the Agricultural Health Study}, volume={125}, ISSN={["1552-9924"]}, DOI={10.1289/ehp1295}, abstractNote={Some epidemiologic and laboratory studies suggest that insecticides are related to increased breast cancer risk, but the evidence is inconsistent. Women engaged in agricultural work or who reside in agricultural areas may experience appreciable exposures to a wide range of insecticides.We examined associations between insecticide use and breast cancer incidence among wives of pesticide applicators (farmers) in the prospective Agricultural Health Study.Farmers and their wives provided information on insecticide use, demographics, and reproductive history at enrollment in 1993-1997 and in 5-y follow-up interviews. Cancer incidence was determined via cancer registries. Among 30,594 wives with no history of breast cancer before enrollment, we examined breast cancer risk in relation to the women's and their husbands' insecticide use using Cox proportional hazards regression to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (CIs).During an average 14.7-y follow-up, 39% of the women reported ever using insecticides, and 1,081 were diagnosed with breast cancer. Although ever use of insecticides overall was not associated with breast cancer risk, risk was elevated among women who had ever used the organophosphates chlorpyrifos [HR=1.4 (95% CI: 1.0, 2.0)] or terbufos [HR=1.5 (95% CI: 1.0, 2.1)], with nonsignificantly increased risks for coumaphos [HR=1.5 (95% CI: 0.9, 2.5)] and heptachlor [HR=1.5 (95% CI: 0.7, 2.9)]. Risk in relation to the wives' use was associated primarily with premenopausal breast cancer. We found little evidence of differential risk by tumor estrogen receptor status. Among women who did not apply pesticides, the husband's use of fonofos was associated with elevated risk, although no exposure-response trend was observed.Use of several organophosphate insecticides was associated with elevated breast cancer risk. However, associations for the women's and husbands' use of these insecticides showed limited concordance. Ongoing cohort follow-up may help clarify the relationship, if any, between individual insecticide exposures and breast cancer risk. https://doi.org/10.1289/EHP1295.}, number={9}, journal={ENVIRONMENTAL HEALTH PERSPECTIVES}, author={Engel, L. S. and Werder, E. and Satagopan, J. and Blair, A. and Hoppin, Jane and Koutros, S. and Lerro, C. C. and Sandler, D. P. and Alavanja, M. C. and Freeman, L. E. B. and et al.}, year={2017}, month={Sep} } @article{bonner_freeman_hoppin_koutros_sandler_lynch_hines_thomas_blair_alavanja_et al._2017, title={Occupational Exposure to Pesticides and the Incidence of Lung Cancer in the Agricultural Health Study}, volume={125}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP456}, DOI={10.1289/ehp456}, abstractNote={Occupational pesticide use is associated with lung cancer in some, but not all, epidemiologic studies. In the Agricultural Health Study (AHS), we previously reported positive associations between several pesticides and lung cancer incidence.We evaluated use of 43 pesticides and 654 lung cancer cases after 10 years of additional follow-up in the AHS, a prospective cohort study comprising 57,310 pesticide applicators from Iowa and North Carolina.Information about lifetime pesticide use and other factors was ascertained at enrollment (1993-1997) and updated with a follow-up questionnaire (1999-2005). Cox proportional hazards models were used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for smoking (smoking status and pack-years), sex, and lifetime days of use of any pesticides.Hazard ratios were elevated in the highest exposure category of lifetime days of use for pendimethalin (1.50; 95% CI: 0.98, 2.31), dieldrin (1.93; 95% CI: 0.70, 5.30), and chlorimuron ethyl (1.74; 95% CI: 1.02, 2.96), although monotonic exposure-response gradients were not evident. The HRs for intensity-weighted lifetime days of use of these pesticides were similar. For parathion, the trend was statistically significant for intensity-weighted lifetime days (p = 0.049) and borderline for lifetime days (p = 0.073). None of the remaining pesticides evaluated was associated with lung cancer incidence.These analyses provide additional evidence for an association between pendimethalin, dieldrin, and parathion use and lung cancer risk. We found an association between chlorimuron ethyl, a herbicide introduced in 1986, and lung cancer that has not been previously reported. Continued follow-up is warranted.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Bonner, M. R. and Freeman, L. E. B. and Hoppin, Jane and Koutros, S. and Sandler, D. P. and Lynch, C. F. and Hines, C. J. and Thomas, K. and Blair, A. and Alavanja, M. C. R. and et al.}, year={2017}, month={Apr}, pages={544–551} } @article{brantsæter_ydersbond_hoppin_haugen_meltzer_2017, title={Organic Food in the Diet: Exposure and Health Implications}, volume={38}, ISSN={0163-7525 1545-2093}, url={http://dx.doi.org/10.1146/annurev-publhealth-031816-044437}, DOI={10.1146/annurev-publhealth-031816-044437}, abstractNote={The market for organic food products is growing rapidly worldwide. Such foods meet certified organic standards for production, handling, processing, and marketing. Most notably, the use of synthetic fertilizers, pesticides, and genetic modification is not allowed. One major reason for the increased demand is the perception that organic food is more environmentally friendly and healthier than conventionally produced food. This review provides an update on market data and consumer preferences for organic food and summarizes the scientific evidence for compositional differences and health benefits of organic compared with conventionally produced food. Studies indicate some differences in favor of organic food, including indications of beneficial health effects. Organic foods convey lower pesticide residue exposure than do conventionally produced foods, but the impact of this on human health is not clear. Comparisons are complicated by organic food consumption being strongly correlated with several indicators of a healthy lifestyle and by conventional agriculture "best practices" often being quite close to those of organic.}, number={1}, journal={Annual Review of Public Health}, publisher={Annual Reviews}, author={Brantsæter, Anne Lise and Ydersbond, Trond A. and Hoppin, Jane A. and Haugen, Margaretha and Meltzer, Helle Margrete}, year={2017}, month={Mar}, pages={295–313} } @article{siegel_starks_sanderson_kamel_hoppin_gerr_2017, title={Organic solvent exposure and depressive symptoms among licensed pesticide applicators in the Agricultural Health Study}, volume={90}, ISSN={0340-0131 1432-1246}, url={http://dx.doi.org/10.1007/s00420-017-1245-8}, DOI={10.1007/s00420-017-1245-8}, abstractNote={Although organic solvents are often used in agricultural operations, neurotoxic effects of solvent exposure have not been extensively studied among farmers. The current analysis examined associations between questionnaire-based metrics of organic solvent exposure and depressive symptoms among farmers. Results from 692 male Agricultural Health Study participants were analyzed. Solvent type and exposure duration were assessed by questionnaire. An “ever-use” variable and years of use categories were constructed for exposure to gasoline, paint/lacquer thinner, petroleum distillates, and any solvent. Depressive symptoms were ascertained with the Center for Epidemiologic Studies Depression Scale (CES-D); scores were analyzed separately as continuous (0–60) and dichotomous (<16 versus ≥16) variables. Multivariate linear and logistic regression models were used to estimate crude and adjusted associations between measures of solvent exposure and CES-D score. Forty-one percent of the sample reported some solvent exposure. The mean CES-D score was 6.5 (SD 6.4; median 5; range 0–44); 92% of the sample had a score below 16. After adjusting for covariates, statistically significant associations were observed between ever-use of any solvent, long duration of any solvent exposure, ever-use of gasoline, ever-use of petroleum distillates, and short duration of petroleum distillate exposure and continuous CES-D score (p < 0.05). Although nearly all associations were positive, fewer statistically significant associations were observed between metrics of solvent exposure and the dichotomized CES-D variable. Solvent exposures were associated with depressive symptoms among farmers. Efforts to limit exposure to organic solvents may reduce the risk of depressive symptoms among farmers.}, number={8}, journal={International Archives of Occupational and Environmental Health}, publisher={Springer Nature}, author={Siegel, Miriam and Starks, Sarah E. and Sanderson, Wayne T. and Kamel, Freya and Hoppin, Jane A. and Gerr, Fred}, year={2017}, month={Jul}, pages={849–857} } @article{hoppin_umbach_long_london_henneberger_blair_alavanja_freeman_sandler_2017, title={Pesticides are Associated with Allergic and Non-Allergic Wheeze among Male Farmers}, volume={125}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP315}, DOI={10.1289/ehp315}, abstractNote={Growing evidence suggests that pesticide use may contribute to respiratory symptoms.We evaluated the association of currently used pesticides with allergic and non-allergic wheeze among male farmers.Using the 2005-2010 interview data of the Agricultural Health Study, a prospective study of farmers in North Carolina and Iowa, we evaluated the association between allergic and non-allergic wheeze and self-reported use of 78 specific pesticides, reported by ≥ 1% of the 22,134 men interviewed. We used polytomous regression models adjusted for age, BMI, state, smoking, and current asthma, as well as for days applying pesticides and days driving diesel tractors. We defined allergic wheeze as reporting both wheeze and doctor-diagnosed hay fever (n = 1,310, 6%) and non-allergic wheeze as reporting wheeze but not hay fever (n = 3,939, 18%); men without wheeze were the referent.In models evaluating current use of specific pesticides, 19 pesticides were significantly associated (p < 0.05) with allergic wheeze (18 positive, 1 negative) and 21 pesticides with non-allergic wheeze (19 positive, 2 negative); 11 pesticides were associated with both. Seven pesticides (herbicides: 2,4-D and simazine; insecticides: carbaryl, dimethoate, disulfoton, and zeta-cypermethrin; and fungicide pyraclostrobin) had significantly different associations for allergic and non-allergic wheeze. In exposure-response models with up to five exposure categories, we saw evidence of an exposure-response relationship for several pesticides including the commonly used herbicides 2,4-D and glyphosate, the insecticides permethrin and carbaryl, and the rodenticide warfarin.These results for farmers implicate several pesticides that are commonly used in agricultural and residential settings with adverse respiratory effects.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, Jane A. and Umbach, David M. and Long, Stuart and London, Stephanie J. and Henneberger, Paul K. and Blair, Aaron and Alavanja, Michael and Freeman, Laura E. Beane and Sandler, Dale P.}, year={2017}, month={Apr}, pages={535–543} } @article{wyss_house_hoppin_richards_hankinson_long_henneberger_beane freeman_sandler_o’connell_et al._2017, title={Raw milk consumption and other early-life farm exposures and adult pulmonary function in the Agricultural Lung Health Study}, volume={73}, ISSN={0040-6376 1468-3296}, url={http://dx.doi.org/10.1136/thoraxjnl-2017-210031}, DOI={10.1136/thoraxjnl-2017-210031}, abstractNote={Literature suggests that early exposure to the farming environment protects against atopy and asthma; few studies have examined pulmonary function. We evaluated associations between early-life farming exposures and pulmonary function in 3061 adults (mean age=63) from a US farming population using linear regression. Childhood raw milk consumption was associated with higher FEV1 (β=49.5 mL, 95% CI 2.8 to 96.1 mL, p=0.04) and FVC (β=66.2 mL, 95% CI 13.2 to 119.1 mL, p=0.01). We did not find appreciable associations with other early-life farming exposures. We report a novel association between raw milk consumption and higher pulmonary function that lasts into older adulthood.}, number={3}, journal={Thorax}, publisher={BMJ}, author={Wyss, Annah B and House, John S and Hoppin, Jane A and Richards, Marie and Hankinson, John L and Long, Stuart and Henneberger, Paul K and Beane Freeman, Laura E and Sandler, Dale P and O’Connell, Elizabeth Long and et al.}, year={2017}, month={Jul}, pages={279–282} } @article{deziel_freeman_graubard_jones_hoppin_thomas_hines_blair_sandler_chen_et al._2017, title={Relative Contributions of Agricultural Drift, Para-Occupational, and Residential Use Exposure Pathways to House Dust Pesticide Concentrations: Meta-Regression of Published Data}, volume={125}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP426}, DOI={10.1289/ehp426}, abstractNote={Increased pesticide concentrations in house dust in agricultural areas have been attributed to several exposure pathways, including agricultural drift, para-occupational, and residential use.To guide future exposure assessment efforts, we quantified relative contributions of these pathways using meta-regression models of published data on dust pesticide concentrations.From studies in North American agricultural areas published from 1995 to 2015, we abstracted dust pesticide concentrations reported as summary statistics [e.g., geometric means (GM)]. We analyzed these data using mixed-effects meta-regression models that weighted each summary statistic by its inverse variance. Dependent variables were either the log-transformed GM (drift) or the log-transformed ratio of GMs from two groups (para-occupational, residential use).For the drift pathway, predicted GMs decreased sharply and nonlinearly, with GMs 64% lower in homes 250 m versus 23 m from fields (interquartile range of published data) based on 52 statistics from seven studies. For the para-occupational pathway, GMs were 2.3 times higher [95% confidence interval (CI): 1.5, 3.3; 15 statistics, five studies] in homes of farmers who applied pesticides more recently or frequently versus less recently or frequently. For the residential use pathway, GMs were 1.3 (95% CI: 1.1, 1.4) and 1.5 (95% CI: 1.2, 1.9) times higher in treated versus untreated homes, when the probability that a pesticide was used for the pest treatment was 1-19% and ≥ 20%, respectively (88 statistics, five studies).Our quantification of the relative contributions of pesticide exposure pathways in agricultural populations could improve exposure assessments in epidemiologic studies. The meta-regression models can be updated when additional data become available. Citation: Deziel NC, Beane Freeman LE, Graubard BI, Jones RR, Hoppin JA, Thomas K, Hines CJ, Blair A, Sandler DP, Chen H, Lubin JH, Andreotti G, Alavanja MC, Friesen MC. 2017. Relative contributions of agricultural drift, para-occupational, and residential use exposure pathways to house dust pesticide concentrations: meta-regression of published data. Environ Health Perspect 125:296-305; http://dx.doi.org/10.1289/EHP426.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Deziel, Nicole C. and Freeman, Laura E. Beane and Graubard, Barry I. and Jones, Rena R. and Hoppin, Jane A. and Thomas, Kent and Hines, Cynthia J. and Blair, Aaron and Sandler, Dale P. and Chen, Honglei and et al.}, year={2017}, month={Mar}, pages={296–305} } @article{grondin_davis_wiegers_king_wiegers_reif_hoppin_mattingly_2016, title={Advancing Exposure Science through Chemical Data Curation and Integration in the Comparative Toxicogenomics Database}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP174}, DOI={10.1289/ehp174}, abstractNote={Exposure science studies the interactions and outcomes between environmental stressors and human or ecological receptors. To augment its role in understanding human health and the exposome, we aimed to centralize and integrate exposure science data into the broader biological framework of the Comparative Toxicogenomics Database (CTD), a public resource that promotes understanding of environmental chemicals and their effects on human health.We integrated exposure data within the CTD to provide a centralized, freely available resource that facilitates identification of connections between real-world exposures, chemicals, genes/proteins, diseases, biological processes, and molecular pathways.We developed a manual curation paradigm that captures exposure data from the scientific literature using controlled vocabularies and free text within the context of four primary exposure concepts: stressor, receptor, exposure event, and exposure outcome. Using data from the Agricultural Health Study, we have illustrated the benefits of both centralization and integration of exposure information with CTD core data.We have described our curation process, demonstrated how exposure data can be accessed and analyzed in the CTD, and shown how this integration provides a broad biological context for exposure data to promote mechanistic understanding of environmental influences on human health.Curation and integration of exposure data within the CTD provides researchers with new opportunities to correlate exposures with human health outcomes, to identify underlying potential molecular mechanisms, and to improve understanding about the exposome.Grondin CJ, Davis AP, Wiegers TC, King BL, Wiegers JA, Reif DM, Hoppin JA, Mattingly CJ. 2016. Advancing exposure science through chemical data curation and integration in the Comparative Toxicogenomics Database. Environ Health Perspect 124:1592-1599; http://dx.doi.org/10.1289/EHP174.}, number={10}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Grondin, Cynthia J. and Davis, Allan Peter and Wiegers, Thomas C. and King, Benjamin L. and Wiegers, Jolene A. and Reif, David M. and Hoppin, Jane A. and Mattingly, Carolyn J.}, year={2016}, month={Oct}, pages={1592–1599} } @article{lubin_albanes_hoppin_chen_lerro_weinstein_sandler_beane freeman_2016, title={Greater Coronary Heart Disease Risk With Lower Intensity and Longer Duration Smoking Compared With Higher Intensity and Shorter Duration Smoking: Congruent Results Across Diverse Cohorts}, volume={19}, ISSN={1462-2203 1469-994X}, url={http://dx.doi.org/10.1093/ntr/ntw290}, DOI={10.1093/ntr/ntw290}, abstractNote={Relative risks (RRs) for coronary heart disease (CHD) by cigarettes/day exhibit a concave pattern, implying the RR increase with each additional cigarette/day consumed decreases with greater intensity. Interpreting this pattern faces limitations, since cigarettes/day alone does not fully characterize smoking-related exposure. A more complete understanding of smoking and CHD risk requires a more comprehensive representation of smoking.}, number={7}, journal={Nicotine & Tobacco Research}, publisher={Oxford University Press (OUP)}, author={Lubin, Jay H. and Albanes, Demetrius and Hoppin, Jane A. and Chen, Honglei and Lerro, Catherine C. and Weinstein, Stephanie J. and Sandler, Dale P. and Beane Freeman, Laura E.}, year={2016}, month={Dec}, pages={ntw290} } @article{rusiecki_beane freeman_bonner_alexander_chen_andreotti_barry_moore_byun_kamel_et al._2016, title={High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study}, volume={58}, ISSN={0893-6692}, url={http://dx.doi.org/10.1002/em.22067}, DOI={10.1002/em.22067}, abstractNote={Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P < 0.01) and for the mean across the CpGs measured in the GSTp1 promoter (P < 0.01). In stratified analyses, elevated GSTP1 promoter DNAm associated with HPEE was more pronounced among applicators >59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction <0.01); HPEE was associated with reduced MGMT promoter DNAm at CpG2 (chr10:131,265,803; P = 0.03), CpG3 (chr10:131,265,810; P = 0.05), and the mean across CpGs measured in the MGMT promoter (P = 0.03) among applicators >59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19-29, 2017. © 2016 Wiley Periodicals, Inc.}, number={1}, journal={Environmental and Molecular Mutagenesis}, publisher={Wiley}, author={Rusiecki, Jennifer A. and Beane Freeman, Laura E. and Bonner, Matthew R. and Alexander, Melannie and Chen, Ligong and Andreotti, Gabriella and Barry, Kathryn H. and Moore, Lee E. and Byun, Hyang-Min and Kamel, Freya and et al.}, year={2016}, month={Dec}, pages={19–29} } @article{brantsæter_torjusen_meltzer_papadopoulou_hoppin_alexander_lieblein_roos_holten_swartz_et al._2016, title={Organic Food Consumption during Pregnancy and Hypospadias and Cryptorchidism at Birth: The Norwegian Mother and Child Cohort Study (MoBa)}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1409518}, DOI={10.1289/ehp.1409518}, abstractNote={The etiologies of the male urogenital anomalies hypospadias and cryptorchidism remain unclear. It has been suggested that maternal diet and environmental contaminants may affect the risk of these anomalies via placental or hormonal disturbances.We examined associations between organic food consumption during pregnancy and prevalence of hypospadias and cryptorchidism at birth.Our study includes 35,107 women participating in the Norwegian Mother and Child Cohort Study (MoBa) who delivered a singleton male infant. Information about use of six groups of organically produced food (vegetables, fruit, bread/cereal, milk/dairy products, eggs, and meat) during pregnancy was collected by a food frequency questionnaire. Women who indicated that they sometimes, often, or mostly consumed organic foods in at least one of the six food groups were classified as organic food consumers in analyses. Hypospadias and cryptorchidism diagnoses were retrieved from the Medical Birth Registry of Norway. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using multiple logistic regression.Seventy-four male newborns were diagnosed with hypospadias (0.2%), and 151 with cryptorchidism (0.4%). Women who consumed any organic food during pregnancy were less likely to give birth to a boy with hypospadias (OR = 0.42; 95% CI: 0.25, 0.70, based on 21 exposed cases) than women who reported they never or seldom consumed organic food. Associations with specific organic foods were strongest for vegetable (OR = 0.36; 95% CI: 0.15, 0.85; 10 exposed cases) and milk/dairy (OR = 0.43; 95% CI: 0.17, 1.07; 7 exposed cases) consumption. No substantial association was observed for consumption of organic food and cryptorchidism.Consumption of organically produced foods during pregnancy was associated with a lower prevalence of hypospadias in our study population. These findings were based on small numbers of cases and require replication in other study populations.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Brantsæter, Anne Lise and Torjusen, Hanne and Meltzer, Helle Margrete and Papadopoulou, Eleni and Hoppin, Jane A. and Alexander, Jan and Lieblein, Geir and Roos, Gun and Holten, Jon Magne and Swartz, Jackie and et al.}, year={2016}, month={Mar}, pages={357–364} } @article{van wendel de joode_mora_lindh_hernández-bonilla_córdoba_wesseling_hoppin_mergler_2016, title={Pesticide exposure and neurodevelopment in children aged 6–9 years from Talamanca, Costa Rica}, volume={85}, ISSN={0010-9452}, url={http://dx.doi.org/10.1016/j.cortex.2016.09.003}, DOI={10.1016/j.cortex.2016.09.003}, abstractNote={Certain pesticides may affect children's neurodevelopment. We assessed whether pesticide exposure was associated with impaired neurobehavioral outcomes in children aged 6–9 years. We conducted a cross-sectional study in 140 children living near banana plantations and plantain farms in the Talamanca County, Costa Rica and assessed their neurobehavioral performance. Exposure was determined by analyzing urinary metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol, TCPy), mancozeb (ethylenethiourea, ETU), and pyrethroids (3-phenoxybenzoic acid, 3-PBA). Repeated urine samples were obtained for 36 children. We estimated associations of pesticide concentrations with neurobehavioral outcomes using multivariable linear and logistic regression models. Median (25th–75th percentiles) TCPy, ETU, and 3-PBA concentrations were 1.4 (.7–3.1), 1.2 (.7–3.0), and .8 (.5–1.5) μg/L, respectively. Intraclass correlation coefficients (ICC) ranged between .32 and .67. After adjustment for potential confounders, higher urinary TCPy concentrations were associated with poorer working memory in boys (n = 59) (β per 10-fold increase in TCPy concentrations = −7.5, 95% CI: −14.4, −.7); poorer visual motor coordination (β = −1.4, 95% CI: −2.7, −.1); increased prevalence of parent-reported cognitive problems/inattention (adjusted OR per 10-fold increase in urinary concentrations = 5.8, 95% CI: 1.6, 22.9), oppositional disorders (aOR = 3.9, 95% CI: 1.0, 16.0), and ADHD (aOR = 6.8, 95% CI: 1.8, 28.6), and; decreased ability to discriminate colors (aOR = 6.6, 95% CI: 1.6, 30.3; the higher the score the worse). Higher ETU concentrations were associated with poorer verbal learning outcomes (β = −7.0, 95% CI: −12.7, −1.3). Higher 3-PBA concentrations were associated with poorer processing speed scores, particularly in girls (β = −8.8, 95% CI: −16.1, −1.4). Our findings indicate that children living near banana and plantain plantations are exposed to pesticides that may affect their neurodevelopment, which for certain domains may differ between boys and girls. We recommend the implementation of measures to reduce pesticide exposure in children living nearby banana plantations.}, journal={Cortex}, publisher={Elsevier BV}, author={van Wendel de Joode, Berna and Mora, Ana M. and Lindh, Christian H. and Hernández-Bonilla, David and Córdoba, Leonel and Wesseling, Catharina and Hoppin, Jane A. and Mergler, Donna}, year={2016}, month={Dec}, pages={137–150} } @article{parks_hoppin_de roos_costenbader_sandler_2016, title={Response to “Comment on ‘Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures’”}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP944}, DOI={10.1289/ehp944}, abstractNote={Vol. 124, No. 11 CorrespondenceOpen AccessResponse to “Comment on ‘Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures’”is a reply to letterComment on “Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures” Christine G. Parks, Jane A. Hoppin, Anneclaire J. De Roos, Karen H. Costenbader, and Dale P. Sandler Christine G. Parks †Address correspondence to C.G. Parks, Epidemiology Branch, A3-05, National Institute of Environmental Health Sciences, PO Box 12233, Research Triangle Park, NC 27599 USA. Telephone: 919-541-2577. E-mail: E-mail Address: [email protected] Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Search for more papers by this author , Jane A. Hoppin Center for Human Health and the Environment, Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA Search for more papers by this author , Anneclaire J. De Roos Department of Environmental and Occupational Health, Drexel University School of Public Health, Philadelphia, Pennsylvania, USA Search for more papers by this author , Karen H. Costenbader Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts, USA. Search for more papers by this author , and Dale P. Sandler Epidemiology Branch, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, North Carolina, USA Search for more papers by this author Published:1 November 2016https://doi.org/10.1289/EHP944AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit We appreciate the comments about our recent paper on pesticides and other farming exposures in relation to rheumatoid arthritis (RA) in female spouses in the Agricultural Health Study (AHS). In their letter, Murphy et al. suggest that heavy metals, such as manganese and cadmium, may account for observed associations of RA with the fungicide maneb/mancozeb and chemical fertilizers, and note other relevant sources of manganese and cadmium exposure. It is intriguing to consider the potential role of metals in RA. As the authors noted, maneb/mancozeb are 21% manganese by weight, and it is possible that this is the relevant active ingredient responsible for the observed association. It is important to note, however, that it is unlikely that metals exposure accounts for the other observed pesticide associations in our study, including those with glyphosate and DDT. In our study sample, maneb/mancozeb use was very uncommon (less than 1% of the cohort and 4% of RA cases) and was not correlated with the other pesticides (e.g., glyphosate, DDT) associated with RA.As Murphy et al. point out, chemical fertilizers may contain cadmium as a contaminant from phosphate mining. This is an important consideration, although levels of cadmium and other metals in commercial products are highly variable (Jiao et al. 2012), so individual exposure levels may be difficult to determine based on self-reported use alone. Other than dietary exposure from foods grown in contaminated soils, there is little known about farmers’ exposure to metals from soil dust. In addition to chemical fertilizers, organic manures may also be a source of heavy metals contributing to increased levels in treated soils (Zhou et al. 2015). In the United States, work in agriculture has been associated with lower urinary cadmium levels compared with several other industries, including repair service, metals manufacturing, construction, and transportation (Yassin and Martonik 2004). Murphy et al. also note that other sources of occupational and nonoccupational metals exposures were associated with RA in our paper.Accurately characterizing metals exposures in the AHS will require considering potential exposures from on- and off-farm jobs, pesticides, fertilizers, and natural sources, e.g., in the soil. We see parallels in assessing another established RA risk factor, crystalline silica (Miller et al. 2012), which occurs naturally in soils, with exposures and silica-related pathology similar to those seen in the “dusty trades” industries (Archer et al. 2002; Schenker et al. 2009). Data needed to assess agricultural silica exposure include tasks performed, crops grown, and soil characteristics (Parks et al. 2003). In the AHS, we expect participants to have a range of exposures to metals such as cadmium, manganese, lead, iron, and arsenic, as well as to silica. Questionnaire data can be used to estimate metals exposures from occupational sources and farm tasks, crops and geocoded farm residence data linked to soil mapping data. Challenges include limited spatial resolution in soil measurements and unmeasurable variation due to fertilizers and other soil amendments (Nicholson et al. 2003). Past practices such as the use of lead arsenate pesticides also may contribute to localized higher concentrations, for example in orchards (Wolz et al. 2003). Soil concentrations of metals and minerals are often correlated because they reflect the composition of the parent rock, highlighting a need to consider multiple exposures (Davis et al. 2009). Future AHS analyses will explore the contribution of occupational factors and soil characteristics to the development of RA, in addition to continued research on the role of pesticides and other farming-related exposures.The authors declare they have no actual or potential competing financial interests.ReferencesArcher JD, Cooper GS, Reist PC, Storm JF, Nylander-French LA. 2002. Exposure to respirable crystalline silica in eastern North Carolina farm workers.AIHA J (Fairfax, Va) 63(6):750-755, PMID: 12570084. Crossref, Medline, Google ScholarDavis HT, Aelion CM, McDermott S, Lawson AB. 2009. Identifying natural and anthropogenic sources of metals in urban and rural soils using GIS-based data, PCA, and spatial interpolation.Environ Pollut 157(8–9):2378-2385, doi:10.1016/j.envpol.2009.03.02119361902. Crossref, Medline, Google ScholarJiao W, Chen W, Chang AC, Page AL. 2012. Environmental risks of trace elements associated with long-term phosphate fertilizers applications: a review.Environ Pollut 168:44-53, doi:10.1016/j.envpol.2012.03.05222591788. Crossref, Medline, Google ScholarMiller FW, Alfredsson L, Costenbader KH, Kamen DL, Nelson LM, Norris JMet al.. 2012. Epidemiology of environmental exposures and human autoimmune diseases: findings from a National Institute of Environmental Health Sciences Expert Panel Workshop.J Autoimmun 39(4):259-271, doi:10.1016/j.jaut.2012.05.00222739348. Crossref, Medline, Google ScholarNicholson FA, Smith SR, Alloway BJ, Carlton-Smith C, Chambers BJ. 2003. An inventory of heavy metals inputs to agricultural soils in England and Wales.Sci Total Environ 311(1–3):205-219, doi:10.1016/S0048-9697(03)00139-612826393. Crossref, Medline, Google ScholarParks CG, Cooper GS, Nylander-French LA, Storm JF, Archer JD. 2003. Assessing exposure to crystalline silica from farm work: a population-based study in the southeastern United States.Ann Epidemiol 13(5):385-392, PMID: 12821278. Crossref, Medline, Google ScholarSchenker MB, Pinkerton KE, Mitchell D, Vallyathan V, Elvine-Kreis B, Green FH. 2009. Pneumoconiosis from agricultural dust exposure among young California farmworkers.Environ Health Perspect 117(6):988-994, doi:10.1289/ehp.080014419590695. Link, Google ScholarWolz S, Fenske RA, Simcox NJ, Palcisko G, Kissel JC. 2003. Residential arsenic and lead levels in an agricultural community with a history of lead arsenate use.Environ Res 93(3):293-300, PMID:. 14615240. Crossref, Medline, Google ScholarYassin AS, Martonik JF. 2004. Urinary cadmium levels in the U S working population, 1988-1994.J Occup Environ Hyg 1(5):324-333, PMID: 15238341. Crossref, Medline, Google ScholarZhou S, Liu J, Xu M, Lv J, Sun N. 2015. Accumulation, availability, and uptake of heavy metals in a red soil after 22-year fertilization and cropping.Environ Sci Pollut Res Intl 22(19):15154-15163, doi:10.1007/s11356-015-4745-7. Crossref, Medline, Google ScholarFiguresReferencesRelatedDetailsRelated articlesComment on “Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures”1 November 2016Environmental Health Perspectives Vol. 124, No. 11 November 2016Metrics About Article Metrics Publication History Originally published1 November 2016Published in print1 November 2016 Financial disclosuresPDF download License information EHP is an open-access journal published with support from the National Institute of Environmental Health Sciences, National Institutes of Health. All content is public domain unless otherwise noted. Note to readers with disabilities EHP strives to ensure that all journal content is accessible to all readers. However, some figures and Supplemental Material published in EHP articles may not conform to 508 standards due to the complexity of the information being presented. If you need assistance accessing journal content, please contact [email protected]. Our staff will work with you to assess and meet your accessibility needs within 3 working days.}, number={11}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Parks, Christine G. and Hoppin, Jane A. and De Roos, Anneclaire J. and Costenbader, Karen H. and Sandler, Dale P.}, year={2016}, month={Nov}, pages={A197–A197} } @article{parks_hoppin_de roos_costenbader_alavanja_sandler_2016, title={Rheumatoid Arthritis in Agricultural Health Study Spouses: Associations with Pesticides and Other Farm Exposures}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/EHP129}, DOI={10.1289/ehp129}, abstractNote={Background:Farming has been associated with rheumatoid arthritis (RA), but the role of pesticides is not known.Objectives:We examined associations between RA and pesticides or other agricultural exposures among female spouses of licensed pesticide applicators in the Agricultural Health Study.Methods:Women were enrolled between 1993 and 1997 and followed through 2010. Cases (n = 275 total, 132 incident), confirmed by a physician or by self-reported use of disease modifying antirheumatic drugs, were compared with noncases (n = 24,018). Odds ratios (OR) and 95% confidence intervals (CI) were estimated using logistic regression models adjusted for age, state, and smoking pack-years.Results:Overall, women with RA were somewhat more likely to have reported lifetime use of any specific pesticide versus no pesticides (OR = 1.4; 95% CI: 1.0, 1.6). Of the 15 pesticides examined, maneb/mancozeb (OR = 3.3; 95% CI: 1.5, 7.1) and glyphosate (OR = 1.4; 95% CI: 1.0, 2.1) were associated with incident RA compared with no pesticide use. An elevated, but non-statistically significant association with incident RA was seen for DDT (OR = 1.9; 95% CI: 0.97, 3.6). Incident RA was also associated with the application of chemical fertilizers (OR = 1.7; 95% CI: 1.1, 2.7) and cleaning with solvents (OR = 1.6; 95% CI: 1.1, 2.4), but inversely associated with lifetime livestock exposure as a child and adult (OR = 0.48; 95% CI: 0.24, 0.97) compared with no livestock exposure.Conclusions:Our results suggest that specific agricultural pesticides, solvents, and chemical fertilizers may increase the risk of RA in women, while exposures involving animal contact may be protective.Citation:Parks CG, Hoppin JA, De Roos AJ, Costenbader KH, Alavanja MC, Sandler DP. 2016. Rheumatoid arthritis in Agricultural Health Study spouses: associations with pesticides and other farm exposures. Environ Health Perspect 124:1728–1734; http://dx.doi.org/10.1289/EHP129}, number={11}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Parks, Christine G. and Hoppin, Jane A. and De Roos, Anneclaire J. and Costenbader, Karen H. and Alavanja, Michael C. and Sandler, Dale P.}, year={2016}, month={Nov}, pages={1728–1734} } @article{jukic_calafat_mcconnaughey_longnecker_hoppin_weinberg_wilcox_baird_calafat_mcconnaughey_et al._2016, title={Urinary Concentrations of Phthalate Metabolites and Bisphenol A and Associations with Follicular-Phase Length, Luteal-Phase Length, Fecundability, and Early Pregnancy Loss}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1408164}, DOI={10.1289/ehp.1408164}, abstractNote={Certain phthalates and bisphenol A (BPA) show reproductive effects in animal studies and potentially affect human ovulation, conception, and pregnancy loss.We investigated these chemicals in relation to follicular- and luteal-phase lengths, time to pregnancy, and early pregnancy loss (within 6 weeks of the last menstrual period) among women attempting pregnancy.Women discontinuing contraception provided daily first-morning urine specimens and recorded days with vaginal bleeding for up to 6 months. Specimens had previously been analyzed for estrogen and progesterone metabolites and human chorionic gonadotropin. A total of 221 participants contributed 706 menstrual cycles. We measured 11 phthalate metabolites and BPA in pooled urine from three specimens spaced throughout each menstrual cycle. We analyzed associations between chemical concentrations and outcomes using linear mixed models for follicular- and luteal-phase lengths, discrete-time fecundability models for time to pregnancy, and logistic regression for early pregnancy loss.Higher concentrations of monocarboxyoctyl phthalate (MCOP) were associated with shorter luteal phase [2nd tertile vs. 1st tertile: -0.5 days (95% CI: -0.9, -0.1), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.01), p = 0.04]. BPA was also associated with shorter luteal phase [2nd vs. 1st: -0.8 days (95% CI: -1.2, -0.4), 3rd vs. 1st: -0.4 days (95% CI: -0.8, 0.02), p = 0.001].BPA and MCOP (or its precursors) were associated with shorter luteal phase. Menstrual cycle-specific estimates of urinary BPA and phthalate metabolites were not associated with detrimental alterations in follicular-phase length, time to pregnancy, or early pregnancy loss, and in fact, DEHP [di(2-ethylhexyl) phthalate] metabolites {MEOHP [mono(2-ethyl-5-oxohexyl) phthalate] and ΣDEHP} were associated with reduced early loss. These findings should be confirmed in future human studies.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Jukic, Anne Marie and Calafat, Antonia M. and McConnaughey, D. Robert and Longnecker, Matthew P. and Hoppin, Jane A. and Weinberg, Clarice R. and Wilcox, Allen J. and Baird, Donna D. and Calafat, Antonia M. and McConnaughey, D. Robert and et al.}, year={2016}, month={Mar}, pages={321–328} } @article{jukic_calafat_mcconnaughey_longnecker_hoppin_weinberg_wilcox_baird_2016, title={Urinary concentrations of phthalate metabolites and bisphenol A and associations with follicular-phase length, luteal-phase length, fecundability, and early pregnancy loss}, volume={124}, number={3}, journal={Environmental Health Perspectives}, author={Jukic, A. M. and Calafat, A. M. and McConnaughey, D. R. and Longnecker, M. P. and Hoppin, J. A. and Weinberg, C. R. and Wilcox, A. J. and Baird, D. D.}, year={2016}, pages={321–328} } @article{tual_silverman_koutros_blair_sandler_lebailly_andreotti_hoppin_freeman_2016, title={Use of Dieselized Farm Equipment and Incident Lung Cancer: Findings from the Agricultural Health Study Cohort}, volume={124}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1409238}, DOI={10.1289/ehp.1409238}, abstractNote={Background:Diesel exhaust is a known lung carcinogen. Farmers use a variety of dieselized equipment and thus may be at increased risk of lung cancer, but farm exposures such as endotoxins may also be protective for lung cancer.Objectives:We evaluated the relative risk of incident lung cancer, including histological subtype, from enrollment (1993–1997) to 2010–2011 in relation to farm equipment use in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators and spouses in Iowa and North Carolina, USA.Methods:Farm equipment use was reported by 21,273 farmers and 29,840 spouses. Rate ratios (RRs) were estimated separately for farmers and spouses with Poisson regression models adjusted for smoking and other confounders. We conducted stratified analyses by exposure to animals or stored grain, a surrogate for endotoxin exposure.Results:Daily diesel tractor use (vs. no use) was positively associated with lung cancer in farmers (RR = 1.48; 95% CI: 0.87, 2.50; 35 exposed, 32 unexposed cases), particularly adenocarcinoma (RR = 3.39; 95% CI: 1.23, 9.33; 12 exposed, 7 unexposed cases). The association of adenocarcinoma with daily (vs. low/no) use of diesel tractors was stronger for farmers with no animal or stored grain exposures (RR = 6.23; 95% CI: 2.25, 17.25; 5 exposed, 18 unexposed cases) than among farmers with these exposures (RR = 1.19; 95% CI: 0.51, 2.79; 7 exposed, 27 unexposed cases) (p-interaction = 0.05).Conclusions:This study provides preliminary evidence of an increased risk of lung adenocarcinoma among daily drivers of diesel tractors and suggests that exposure to endotoxins may modify the impact of diesel exposure on lung cancer risk. Confirmation of these findings with more exposed cases and more detailed exposure information is warranted.Citation:Tual S, Silverman DT, Koutros S, Blair A, Sandler DP, Lebailly P, Andreotti G, Hoppin JA, Beane Freeman LE. 2016. Use of dieselized farm equipment and incident lung cancer: findings from the Agricultural Health Study Cohort. Environ Health Perspect 124:611–618; http://dx.doi.org/10.1289/ehp.1409238}, number={5}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Tual, Séverine and Silverman, Debra T. and Koutros, Stella and Blair, Aaron and Sandler, Dale P. and Lebailly, Pierre and Andreotti, Gabriella and Hoppin, Jane A. and Freeman, Laura E. Beane}, year={2016}, month={May}, pages={611–618} } @article{deziel_friesen_hoppin_hines_thomas_freeman_2015, title={A Review of Nonoccupational Pathways for Pesticide Exposure in Women Living in Agricultural Areas}, volume={123}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1408273}, DOI={10.1289/ehp.1408273}, abstractNote={Women living in agricultural areas may experience high pesticide exposures compared with women in urban or suburban areas because of their proximity to farm activities.Our objective was to review the evidence in the published literature for the contribution of nonoccupational pathways of pesticide exposure in women living in North American agricultural areas.We evaluated the following nonoccupational exposure pathways: paraoccupational (i.e., take-home or bystander exposure), agricultural drift, residential pesticide use, and dietary ingestion. We also evaluated the role of hygiene factors (e.g., house cleaning, shoe removal).Among 35 publications identified (published 1995-2013), several reported significant or suggestive (p < 0.1) associations between paraoccupational (n = 19) and agricultural drift (n = 10) pathways and pesticide dust or biomarker levels, and 3 observed that residential use was associated with pesticide concentrations in dust. The 4 studies related to ingestion reported low detection rates of most pesticides in water; additional studies are needed to draw conclusions about the importance of this pathway. Hygiene factors were not consistently linked to exposure among the 18 relevant publications identified.Evidence supported the importance of paraoccupational, drift, and residential use pathways. Disentangling exposure pathways was difficult because agricultural populations are concurrently exposed to pesticides via multiple pathways. Most evidence was based on measurements of pesticides in residential dust, which are applicable to any household member and are not specific to women. An improved understanding of nonoccupational pesticide exposure pathways in women living in agricultural areas is critical for studying health effects in women and for designing effective exposure-reduction strategies.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Deziel, Nicole C. and Friesen, Melissa C. and Hoppin, Jane A. and Hines, Cynthia J. and Thomas, Kent and Freeman, Laura E. Beane}, year={2015}, month={Jun}, pages={515–524} } @article{kirrane_bowman_davis_hoppin_blair_chen_patel_sandler_tanner_vinikoor-imler_et al._2015, title={Associations of Ozone and PM2.5 Concentrations With Parkinsonʼs Disease Among Participants in the Agricultural Health Study}, volume={57}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0000000000000451}, DOI={10.1097/JOM.0000000000000451}, abstractNote={Objective: This study describes associations of ozone and fine particulate matter with Parkinson's disease observed among farmers in North Carolina and Iowa. Methods: We used logistic regression to determine the associations of these pollutants with self-reported, doctor-diagnosed Parkinson's disease. Daily predicted pollutant concentrations were used to derive surrogates of long-term exposure and link them to study participants' geocoded addresses. Results: We observed positive associations of Parkinson's disease with ozone (odds ratio = 1.39; 95% CI: 0.98 to 1.98) and fine particulate matter (odds ratio = 1.34; 95% CI: 0.93 to 1.93) in North Carolina but not in Iowa. Conclusions: The plausibility of an effect of ambient concentrations of these pollutants on Parkinson's disease risk is supported by experimental data demonstrating damage to dopaminergic neurons at relevant concentrations. Additional studies are needed to address uncertainties related to confounding and to examine temporal aspects of the associations we observed.}, number={5}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Kirrane, Ellen F. and Bowman, Christal and Davis, J. Allen and Hoppin, Jane A. and Blair, Aaron and Chen, Honglei and Patel, Molini M. and Sandler, Dale P. and Tanner, Caroline M. and Vinikoor-Imler, Lisa and et al.}, year={2015}, month={May}, pages={509–517} } @article{silver_bertke_hines_alavanja_hoppin_lubin_rusiecki_sandler_beane freeman_2015, title={Cancer incidence and metolachlor use in the Agricultural Health Study: An update}, volume={137}, ISSN={0020-7136}, url={http://dx.doi.org/10.1002/ijc.29621}, DOI={10.1002/ijc.29621}, abstractNote={Metolachlor, a widely used herbicide, is classified as a Group C carcinogen by the U.S. Environmental Protection Agency based on increased liver neoplasms in female rats. Epidemiologic studies of the health effects of metolachlor have been limited. The Agricultural Health Study (AHS) is a prospective cohort study including licensed private and commercial pesticide applicators in Iowa and North Carolina enrolled 1993–1997. We evaluated cancer incidence through 2010/2011 (NC/IA) for 49,616 applicators, 53% of whom reported ever using metolachlor. We used Poisson regression to evaluate relations between two metrics of metolachlor use (lifetime days, intensity‐weighted lifetime days) and cancer incidence. We saw no association between metolachlor use and incidence of all cancers combined ( n = 5,701 with a 5‐year lag) or most site‐specific cancers. For liver cancer, in analyses restricted to exposed workers, elevations observed at higher categories of use were not statistically significant. However, trends for both lifetime and intensity‐weighted lifetime days of metolachor use were positive and statistically significant with an unexposed reference group. A similar pattern was observed for follicular cell lymphoma, but no other lymphoma subtypes. An earlier suggestion of increased lung cancer risk at high levels of metolachlor use in this cohort was not confirmed in this update. This suggestion of an association between metolachlor and liver cancer among pesticide applicators is a novel finding and echoes observation of increased liver neoplasms in some animal studies. However, our findings for both liver cancer and follicular cell lymphoma warrant follow‐up to better differentiate effects of metolachlor use from other factors.}, number={11}, journal={International Journal of Cancer}, publisher={Wiley}, author={Silver, Sharon R. and Bertke, Steven J. and Hines, Cynthia J. and Alavanja, Michael C.R. and Hoppin, Jane A. and Lubin, Jay H. and Rusiecki, Jennifer A. and Sandler, Dale P. and Beane Freeman, Laura E.}, year={2015}, month={Jun}, pages={2630–2643} } @article{igartua_myers_mathias_pino-yanes_eng_graves_levin_del-rio-navarro_jackson_livne_et al._2015, title={Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma}, volume={6}, ISSN={2041-1723}, url={http://dx.doi.org/10.1038/ncomms6965}, DOI={10.1038/ncomms6965}, abstractNote={Abstract Common variants at many loci have been robustly associated with asthma but explain little of the overall genetic risk. Here we investigate the role of rare (<1%) and low-frequency (1–5%) variants using the Illumina HumanExome BeadChip array in 4,794 asthma cases, 4,707 non-asthmatic controls and 590 case–parent trios representing European Americans, African Americans/African Caribbeans and Latinos. Our study reveals one low-frequency missense mutation in the GRASP gene that is associated with asthma in the Latino sample ( P =4.31 × 10 −6 ; OR=1.25; MAF=1.21%) and two genes harbouring functional variants that are associated with asthma in a gene-based analysis: GSDMB at the 17q12–21 asthma locus in the Latino and combined samples ( P =7.81 × 10 −8 and 4.09 × 10 −8 , respectively) and MTHFR in the African ancestry sample ( P =1.72 × 10 −6 ). Our results suggest that associations with rare and low-frequency variants are ethnic specific and not likely to explain a significant proportion of the ‘missing heritability’ of asthma.}, number={1}, journal={Nature Communications}, publisher={Springer Science and Business Media LLC}, author={Igartua, Catherine and Myers, Rachel A. and Mathias, Rasika A. and Pino-Yanes, Maria and Eng, Celeste and Graves, Penelope E. and Levin, Albert M. and Del-Rio-Navarro, Blanca E. and Jackson, Daniel J. and Livne, Oren E. and et al.}, year={2015}, month={Jan} } @article{igartua_myers_mathias_pino-yanes_eng_graves_levin_del-rio-navarro_jackson_livne_et al._2015, title={Ethnic-specific associations of rare and low-frequency DNA sequence variants with asthma}, volume={6}, journal={Nature Communications}, author={Igartua, C. and Myers, R. A. and Mathias, R. A. and Pino-Yanes, M. and Eng, C. and Graves, P. E. and Levin, A. M. and Del-Rio-Navarro, B. E. and Jackson, D. J. and Livne, O. E. and et al.}, year={2015} } @article{hofmann_hoppin_lynch_poole_purdue_blair_alavanja_beane freeman_2015, title={Farm Characteristics, Allergy Symptoms, and Risk of Non-Hodgkin Lymphoid Neoplasms in the Agricultural Health Study}, volume={24}, ISSN={1055-9965 1538-7755}, url={http://dx.doi.org/10.1158/1055-9965.EPI-14-1246}, DOI={10.1158/1055-9965.epi-14-1246}, abstractNote={Because of unique exposures, studies among farmers may yield insights into the relationship between allergies and non-Hodgkin lymphoid (NHL) neoplasms. We evaluated farm characteristics, allergic symptoms and conditions, and risk of NHL including specific subtypes in the Agricultural Health Study, a prospective cohort of farmers and spouses from North Carolina and Iowa.We identified 710 incident cases of NHL (including chronic lymphocytic leukemia and multiple myeloma) among 82,370 participants with baseline data on crop and animal exposures, including 454 cases among 52,850 participants with baseline data on recent allergy symptoms (rhinitis) and living on a farm during childhood. HR and 95% confidence intervals (CI) were calculated using multivariable-adjusted proportional hazards models.We observed reduced risks of NHL among farmers and spouses with rhinitis at baseline (HR, 0.63; 95% CI, 0.51-0.79), related to growing soybeans (HR, 0.80; 95% CI, 0.67-0.96), and among farmers who handled stored grains or hay (HR, 0.66; 95% CI, 0.52-0.82). Growing up on a farm was associated with increased NHL risk (HR, 1.51; 95% CI, 1.15-1.98). Results did not differ significantly by NHL subtype.Both the reduced risk of NHL among those with allergy symptoms and specific farm exposures in adulthood, and the increased risk among those who grew up on a farm suggest that the host immune response to agricultural allergens may influence NHL development.This prospective study is, to our knowledge, the first to investigate the relationship between allergy symptoms and NHL risk in farmers; confirmation of these findings in other farming populations is warranted. Cancer Epidemiol Biomarkers Prev; 24(3); 587-94. ©2015 AACR.}, number={3}, journal={Cancer Epidemiology Biomarkers & Prevention}, publisher={American Association for Cancer Research (AACR)}, author={Hofmann, J. N. and Hoppin, J. A. and Lynch, C. F. and Poole, J. A. and Purdue, M. P. and Blair, A. and Alavanja, M. C. and Beane Freeman, L. E.}, year={2015}, month={Jan}, pages={587–594} } @article{pearce_blair_vineis_ahrens_andersen_anto_armstrong_baccarelli_beland_berrington_et al._2015, title={IARC Monographs: 40 Years of Evaluating Carcinogenic Hazards to Humans}, volume={123}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1409149}, DOI={10.1289/ehp.1409149}, abstractNote={Background: Recently, the International Agency for Research on Cancer (IARC) Programme for the Evaluation of Carcinogenic Risks to Humans has been criticized for several of its evaluations, and also for the approach used to perform these evaluations. Some critics have claimed that failures of IARC Working Groups to recognize study weaknesses and biases of Working Group members have led to inappropriate classification of a number of agents as carcinogenic to humans.Objectives: The authors of this Commentary are scientists from various disciplines relevant to the identification and hazard evaluation of human carcinogens. We examined criticisms of the IARC classification process to determine the validity of these concerns. Here, we present the results of that examination, review the history of IARC evaluations, and describe how the IARC evaluations are performed.Discussion: We concluded that these recent criticisms are unconvincing. The procedures employed by IARC to assemble Working Groups of scientists from the various disciplines and the techniques followed to review the literature and perform hazard assessment of various agents provide a balanced evaluation and an appropriate indication of the weight of the evidence. Some disagreement by individual scientists to some evaluations is not evidence of process failure. The review process has been modified over time and will undoubtedly be altered in the future to improve the process. Any process can in theory be improved, and we would support continued review and improvement of the IARC processes. This does not mean, however, that the current procedures are flawed.Conclusions: The IARC Monographs have made, and continue to make, major contributions to the scientific underpinning for societal actions to improve the public's health.Citation: Pearce N, Blair A, Vineis P, Ahrens W, Andersen A, Anto JM, Armstrong BK, Baccarelli AA, Beland FA, Berrington A, Bertazzi PA, Birnbaum LS, Brownson RC, Bucher JR, Cantor KP, Cardis E, Cherrie JW, Christiani DC, Cocco P, Coggon D, Comba P, Demers PA, Dement JM, Douwes J, Eisen EA, Engel LS, Fenske RA, Fleming LE, Fletcher T, Fontham E, Forastiere F, Frentzel-Beyme R, Fritschi L, Gerin M, Goldberg M, Grandjean P, Grimsrud TK, Gustavsson P, Haines A, Hartge P, Hansen J, Hauptmann M, Heederik D, Hemminki K, Hemon D, Hertz-Picciotto I, Hoppin JA, Huff J, Jarvholm B, Kang D, Karagas MR, Kjaerheim K, Kjuus H, Kogevinas M, Kriebel D, Kristensen P, Kromhout H, Laden F, Lebailly P, LeMasters G, Lubin JH, Lynch CF, Lynge E, 't Mannetje A, McMichael AJ, McLaughlin JR, Marrett L, Martuzzi M, Merchant JA, Merler E, Merletti F, Miller A, Mirer FE, Monson R, Nordby KC, Olshan AF, Parent ME, Perera FP, Perry MJ, Pesatori AC, Pirastu R, Porta M, Pukkala E, Rice C, Richardson DB, Ritter L, Ritz B, Ronckers CM, Rushton L, Rusiecki JA, Rusyn I, Samet JM, Sandler DP, de Sanjose S, Schernhammer E, Seniori Costantini A, Seixas N, Shy C, Siemiatycki J, Silverman DT, Simonato L, Smith AH, Smith MT, Spinelli JJ, Spitz MR, Stallones L, Stayner LT, Steenland K, Stenzel M, Stewart BW, Stewart PA, Symanski E, Terracini B, Tolbert PE, Vainio H, Vena J, Vermeulen R, Victora CG, Ward EM, Weinberg CR, Weisenburger D, Wesseling C, Weiderpass E, Zahm SH. 2015. IARC Monographs: 40 years of evaluating carcinogenic hazards to humans. Environ Health Perspect 123:507–514; http://dx.doi.org/10.1289/ehp.1409149}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Pearce, Neil and Blair, Aaron and Vineis, Paolo and Ahrens, Wolfgang and Andersen, Aage and Anto, Josep M. and Armstrong, Bruce K. and Baccarelli, Andrea A. and Beland, Frederick A. and Berrington, Amy and et al.}, year={2015}, month={Jun}, pages={507–514} } @article{iarc monographs: 40 years of evaluating carcinogenic hazards to humans_2015, volume={123}, number={6}, journal={Environmental Health Perspectives}, year={2015}, pages={507–514} } @article{jones_barone-adesi_koutros_lerro_blair_lubin_heltshe_hoppin_alavanja_freeman_et al._2015, title={Incidence of solid tumours among pesticide applicators exposed to the organophosphate insecticide diazinon in the Agricultural Health Study: an updated analysis}, volume={72}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2014-102728}, DOI={10.1136/oemed-2014-102728}, abstractNote={

Objective

Diazinon, a common organophosphate insecticide with genotoxic properties, was previously associated with lung cancer in the Agricultural Health Study (AHS) cohort, but few other epidemiological studies have examined diazinon-associated cancer risk. We used updated diazinon exposure and cancer incidence information to evaluate solid tumour risk in the AHS.

Methods

Male pesticide applicators in Iowa and North Carolina reported lifetime diazinon use at enrolment (1993–1997) and follow-up (1998–2005); cancer incidence was assessed through 2010(North Carolina)/2011(Iowa). Among applicators with usage information sufficient to evaluate exposure-response patterns, we used Poisson regression to estimate adjusted rate ratios (RRs) and 95% CI for cancer sites with ≥10 exposed cases for both lifetime (LT) exposure days and intensity-weighted (IW) lifetime exposure days (accounting for factors impacting exposure).

Results

We observed elevated lung cancer risks (N=283) among applicators with the greatest number of LT (RR=1.60; 95% CI 1.11 to 2.31; Ptrend=0.02) and IW days of diazinon use (RR=1.41; 95% CI 0.98 to 2.04; Ptrend=0.08). Kidney cancer (N=94) risks were non-significantly elevated (RRLT days=1.77; 95% CI 0.90 to 3.51; Ptrend=0.09; RRIW days 1.37; 95% CI 0.64 to 2.92; Ptrend=0.50), as were risks for aggressive prostate cancer (N=656).

Conclusions

Our updated evaluation of diazinon provides additional evidence of an association with lung cancer risk. Newly identified links to kidney cancer and associations with aggressive prostate cancer require further evaluation.}, number={7}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Jones, R. R. and Barone-Adesi, F. and Koutros, S. and Lerro, C. C. and Blair, A. and Lubin, J. and Heltshe, S. L. and Hoppin, Jane and Alavanja, M. C. R. and Freeman, L. E. B. and et al.}, year={2015}, month={Apr}, pages={496–503} } @article{blair_hines_thomas_alavanja_freeman_hoppin_kamel_lynch_lubin_silverman_et al._2015, title={Investing in prospective cohorts for etiologic study of occupational exposures}, volume={58}, ISSN={0271-3586}, url={http://dx.doi.org/10.1002/ajim.22403}, DOI={10.1002/ajim.22403}, abstractNote={Prospective cohorts have played a major role in understanding the contribution of diet, physical activity, medical conditions, and genes to the development of many diseases, but have not been widely used for occupational exposures. Studies in agriculture are an exception. We draw upon our experience using this design to study agricultural workers to identify conditions that might foster use of prospective cohorts to study other occupational settings. Prospective cohort studies are perceived by many as the strongest epidemiologic design. It allows updating of information on exposure and other factors, collection of biologic samples before disease diagnosis for biomarker studies, assessment of effect modification by genes, lifestyle, and other occupational exposures, and evaluation of a wide range of health outcomes. Increased use of prospective cohorts would be beneficial in identifying hazardous exposures in the workplace. Occupational epidemiologists should seek opportunities to initiate prospective cohorts to investigate high priority, occupational exposures. Am. J. Ind. Med. 58:113–122, 2015. © 2015 Wiley Periodicals, Inc.}, number={2}, journal={American Journal of Industrial Medicine}, publisher={Wiley}, author={Blair, A. and Hines, C.J. and Thomas, K.W. and Alavanja, M.C.R. and Freeman, L.E. Beane and Hoppin, J.A. and Kamel, F. and Lynch, C.F. and Lubin, J.H. and Silverman, D.T. and et al.}, year={2015}, month={Jan}, pages={113–122} } @article{jacob_hoppin_steers_davis_davidson_hansen_lunn_murphy_papich_2015, title={Opinions of clinical veterinarians at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections}, volume={247}, ISSN={0003-1488}, url={http://dx.doi.org/10.2460/javma.247.8.938}, DOI={10.2460/javma.247.8.938}, abstractNote={To determine opinions of faculty members with clinical appointments, clinical veterinarians, residents, and interns at a US veterinary teaching hospital regarding antimicrobial use and antimicrobial-resistant infections.Cross-sectional survey.71 veterinarians.An online questionnaire was sent to all veterinarians with clinical service responsibilities at the North Carolina State University veterinary teaching hospital (n = 167). The survey included 23 questions regarding demographic information, educational experiences, current prescribing practices, and personal opinions related to antimicrobial selection, antimicrobial use, restrictions on antimicrobial use, and antimicrobial resistance.Of the 167 veterinarians eligible to participate, 71 (43%) responded. When respondents were asked to rate their level of concern (very concerned = 1; not concerned = 5) about antimicrobial-resistant infections, most (41/70 [59%]) assigned a score of 1, with mean score for all respondents being 1.5. Most survey participants rated their immediate colleagues (mean score, 1.9) as more concerned than other veterinary medical professionals (mean score, 2.3) and their clients (mean score, 3.4). Fifty-nine of 67 (88%) respondents felt that antimicrobials were overprescribed at the hospital, and 32 of 69 (46%) respondents felt uncomfortable prescribing at least one class of antimicrobials (eg, carbapenems or glycopeptides) because of public health concerns.Findings indicated that veterinarians at this teaching hospital were concerned about antimicrobial resistance, thought antimicrobials were overprescribed, and supported restricting use of certain antimicrobial classes in companion animals. Findings may be useful in educating future veterinarians and altering prescribing habits and antimicrobial distribution systems in veterinary hospitals.}, number={8}, journal={Journal of the American Veterinary Medical Association}, publisher={American Veterinary Medical Association (AVMA)}, author={Jacob, Megan E. and Hoppin, Jane A. and Steers, Nicola and Davis, Jennifer L. and Davidson, Gigi and Hansen, Bernie and Lunn, Katharine F. and Murphy, K. Marcia and Papich, Mark G.}, year={2015}, month={Oct}, pages={938–944} } @article{lerro_koutros_andreotti_friesen_alavanja_blair_hoppin_sandler_lubin_ma_et al._2015, title={Organophosphate insecticide use and cancer incidence among spouses of pesticide applicators in the Agricultural Health Study}, volume={72}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2014-102798}, DOI={10.1136/oemed-2014-102798}, abstractNote={

Objectives

Organophosphates (OPs) are among the most commonly used insecticides. OPs have been linked to cancer risk in some epidemiological studies, which have been largely conducted in predominantly male populations. We evaluated personal use of specific OPs and cancer incidence among female spouses of pesticide applicators in the prospective Agricultural Health Study cohort.

Methods

At enrolment (1993–1997), spouses provided information about ever use of specific pesticides, including 10 OPs, demographic information, reproductive health history and other potential confounders. We used Poisson regression to estimate relative risks (RRs) and 95% CIs for all cancers diagnosed through 2010 for North Carolina and through 2011 for Iowa.

Results

Among 30 003 women, 25.9% reported OP use, and 718 OP-exposed women were diagnosed with cancer during the follow-up period. Any OP use was associated with an elevated risk of breast cancer (RR=1.20, 95% CI 1.01 to 1.43). Malathion, the most commonly reported OP, was associated with increased risk of thyroid cancer (RR=2.04, 95% CI 1.14 to 3.63) and decreased risk of non-Hodgkin lymphoma (RR=0.64, 95% CI 0.41 to 0.99). Diazinon use was associated with ovarian cancer (RR=1.87, 95% CI 1.02 to 3.43).

Conclusions

We observed increased risk with OP use for several hormonally-related cancers, including breast, thyroid and ovary, suggesting potential for hormonally-mediated effects. This study represents the first comprehensive analysis of OP use and cancer risk among women, and thus demonstrates a need for further evaluation.}, number={10}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Lerro, Catherine C and Koutros, Stella and Andreotti, Gabriella and Friesen, Melissa C and Alavanja, Michael C and Blair, Aaron and Hoppin, Jane A and Sandler, Dale P and Lubin, Jay H and Ma, Xiaomei and et al.}, year={2015}, month={Jul}, pages={736–744} } @article{andreotti_hoppin_hou_koutros_gadalla_savage_lubin_blair_hoxha_baccarelli_et al._2015, title={Pesticide Use and Relative Leukocyte Telomere Length in the Agricultural Health Study}, volume={10}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0133382}, DOI={10.1371/journal.pone.0133382}, abstractNote={Some studies suggest that telomere length (TL) may be influenced by environmental exposures, including pesticides. We examined associations between occupational pesticide use reported at three time points and relative telomere length (RTL) in the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators in Iowa and North Carolina. RTL was measured by qPCR using leukocyte DNA from 568 cancer-free male AHS participants aged 31-94 years with blood samples collected between 2006 and 2008. Self-reported information, including pesticide use, was collected at three time points: enrollment (1993-1997) and two follow-up questionnaires (1998-2003, 2005-2008). For each pesticide, we evaluated cumulative use (using data from all three questionnaires), and more recent use (using data from the last follow-up questionnaire). Multivariable linear regression was used to examine the associations between pesticide use (ever, lifetime days, intensity-weighted lifetime days (lifetime days*intensity score)) and RTL, adjusting for age at blood draw and use of other pesticides. Of the 57 pesticides evaluated with cumulative use, increasing lifetime days of 2,4-D (p-trend=0.001), diazinon (p-trend=0.002), and butylate (p-trend=0.01) were significantly associated with shorter RTL, while increasing lifetime days of alachlor was significantly associated with longer RTL (p-trend=0.03). Only the association with 2,4-D was significant after adjustment for multiple comparisons. Of the 40 pesticides evaluated for recent use, malathion was associated with shorter RTL (p=0.03), and alachlor with longer RTL (p=0.03). Our findings suggest that leukocyte TL may be impacted by cumulative use and recent use of certain pesticides.}, number={7}, journal={PLOS ONE}, publisher={Public Library of Science (PLoS)}, author={Andreotti, Gabriella and Hoppin, Jane A. and Hou, Lifang and Koutros, Stella and Gadalla, Shahinaz M. and Savage, Sharon A. and Lubin, Jay and Blair, Aaron and Hoxha, Mirjam and Baccarelli, Andrea and et al.}, editor={Nawrot, Tim S.Editor}, year={2015}, month={Jul}, pages={e0133382} } @article{lebov_engel_richardson_hogan_sandler_hoppin_2015, title={Pesticide exposure and end-stage renal disease risk among wives of pesticide applicators in the Agricultural Health Study}, volume={143}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2015.10.002}, DOI={10.1016/j.envres.2015.10.002}, abstractNote={Pesticide exposure has been found to cause renal damage and dysfunction in experimental studies, but epidemiological research on the renal effects of chronic low-level pesticide exposure is limited. We investigated the relationships between end-stage renal disease (ESRD) among wives of licensed pesticide applicators (N=31,142) in the Agricultural Health Study (AHS) and (1) personal pesticide use, (2) exposure to the husband's pesticide use, and (3) other pesticide-associated farming and household activities. AHS participants reported pesticide exposure via self-administered questionnaires at enrollment (1993–1997). ESRD cases were identified via linkage to the United States Renal Data System. Associations between ESRD and pesticide exposures were estimated with Cox proportional hazard regression models controlling for age at enrollment. Models of associations with farming and household factors were additionally adjusted for personal use of pesticides. We identified 98 ESRD cases diagnosed between enrollment and 31 December 2011. Although women who ever applied pesticides (56% of cohort) were less likely than those who did not apply to develop ESRD (Hazard Ratio (HR): 0.42; 95% CI: 0.28, 0.64), among women who did apply pesticides, the rate of ESRD was significantly elevated among those who reported the highest (vs. lowest) cumulative general pesticide use (HR: 4.22; 95% CI: 1.26, 14.20). Among wives who never applied pesticides, ESRD was associated with husbands' ever use of paraquat (HR=1.99; 95% CI: 1.14, 3.47) and butylate (HR=1.71; 95% CI: 1.00, 2.95), with a positive exposure–response pattern for husband’s cumulative use of these pesticides. ESRD may be associated with direct and/or indirect exposure to pesticides among farm women. Future studies should evaluate indirect exposure risk among other rural populations.}, journal={Environmental Research}, publisher={Elsevier BV}, author={Lebov, Jill F. and Engel, Lawrence S. and Richardson, David and Hogan, Susan L. and Sandler, Dale P. and Hoppin, Jane A.}, year={2015}, month={Nov}, pages={198–210} } @article{lebov_engel_richardson_hogan_hoppin_sandler_2015, title={Pesticide use and risk of end-stage renal disease among licensed pesticide applicators in the Agricultural Health Study}, volume={73}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2014-102615}, DOI={10.1136/oemed-2014-102615}, abstractNote={

Objectives

Experimental studies suggest a relationship between pesticide exposure and renal impairment, but epidemiological evidence is limited. We evaluated the association between exposure to 39 specific pesticides and end-stage renal disease (ESRD) incidence in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.

Methods

Via linkage to the US Renal Data System, we identified 320 ESRD cases diagnosed between enrolment (1993–1997) and December 2011 among 55 580 male licensed pesticide applicators. Participants provided information on use of pesticides via self-administered questionnaires. Lifetime pesticide use was defined as the product of duration and frequency of use and then modified by an intensity factor to account for differences in pesticide application practices. Cox proportional hazards models, adjusted for age and state, were used to estimate associations between ESRD and: (1) ordinal categories of intensity-weighted lifetime use of 39 pesticides, (2) poisoning and high-level pesticide exposures and (3) pesticide exposure resulting in a medical visit or hospitalisation.

Results

Positive exposure-response trends were observed for the herbicides alachlor, atrazine, metolachlor, paraquat, and pendimethalin, and the insecticide permethrin. More than one medical visit due to pesticide use (HR=2.13; 95% CI 1.17 to 3.89) and hospitalisation due to pesticide use (HR=3.05; 95% CI 1.67 to 5.58) were significantly associated with ESRD.

Conclusions

Our findings support an association between ESRD and chronic exposure to specific pesticides, and suggest pesticide exposures resulting in medical visits may increase the risk of ESRD.

Clinical trial registration

Clinicaltrials.gov NCT00352924.}, number={1}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Lebov, Jill F and Engel, Lawrence S and Richardson, David and Hogan, Susan L and Hoppin, Jane A and Sandler, Dale P}, year={2015}, month={Jul}, pages={3–12} } @article{furlong_tanner_goldman_bhudhikanok_blair_chade_comyns_hoppin_kasten_korell_et al._2015, title={Protective glove use and hygiene habits modify the associations of specific pesticides with Parkinson's disease}, volume={75}, ISSN={0160-4120}, url={http://dx.doi.org/10.1016/j.envint.2014.11.002}, DOI={10.1016/j.envint.2014.11.002}, abstractNote={Pesticides have been associated with Parkinson's disease (PD), and protective gloves and workplace hygiene can reduce pesticide exposure. We assessed whether use of gloves and workplace hygiene modified associations between pesticides and PD. The Farming and Movement Evaluation (FAME) study is a nested case-control study within the Agricultural Health Study. Use of protective gloves, other PPE, and hygiene practices were determined by questionnaire (69 cases and 237 controls were included). We considered interactions of gloves and hygiene with ever-use of pesticides for all pesticides with ≥5 exposed and unexposed cases and controls in each glove-use stratum (paraquat, permethrin, rotenone, and trifluralin). 61% of respondents consistently used protective gloves and 87% consistently used ≥2 hygiene practices. Protective glove use modified the associations of paraquat and permethrin with PD: neither pesticide was associated with PD among protective glove users, while both pesticides were associated with PD among non-users (paraquat OR 3.9 [95% CI 1.3, 11.7], interaction p=0.15; permethrin OR 4.3 [95% CI 1.2, 15.6] interaction p=0.05). Rotenone was associated with PD regardless of glove use. Trifluralin was associated with PD among participants who used <2 hygiene practices (OR 5.5 [95% CI 1.1, 27.1]) but was not associated with PD among participants who used 2 or more practices (interaction p=0.02). Although sample size was limited in the FAME study, protective glove use and hygiene practices appeared to be important modifiers of the association between pesticides and PD and may reduce risk of PD associated with certain pesticides.}, journal={Environment International}, publisher={Elsevier BV}, author={Furlong, Melissa and Tanner, Caroline M. and Goldman, Samuel M. and Bhudhikanok, Grace S. and Blair, Aaron and Chade, Anabel and Comyns, Kathleen and Hoppin, Jane A. and Kasten, Meike and Korell, Monica and et al.}, year={2015}, month={Feb}, pages={144–150} } @article{jones_dellavalle_flory_nordan_hoppin_hofmann_chen_giglierano_lynch_beane freeman_et al._2014, title={Accuracy of residential geocoding in the Agricultural Health Study}, volume={13}, ISSN={1476-072X}, url={http://dx.doi.org/10.1186/1476-072X-13-37}, DOI={10.1186/1476-072x-13-37}, abstractNote={Environmental exposure assessments often require a study participant's residential location, but the positional accuracy of geocoding varies by method and the rural status of an address. We evaluated geocoding error in the Agricultural Health Study (AHS), a cohort of pesticide applicators and their spouses in Iowa and North Carolina, U.S.A. For 5,064 AHS addresses in Iowa, we compared rooftop coordinates as a gold standard to two alternate locations: 1) E911 locations (intersection of the private and public road), and 2) geocodes generated by matching addresses to a commercial street database (NAVTEQ) or placed manually. Positional error (distance in meters (m) from the rooftop) was assessed overall and separately for addresses inside (non-rural) or outside town boundaries (rural). We estimated the sensitivity and specificity of proximity-based exposures (crops, animal feeding operations (AFOs)) and the attenuation in odds ratios (ORs) for a hypothetical nested case–control study. We also evaluated geocoding errors within two AHS subcohorts in Iowa and North Carolina by comparing them to GPS points taken at residences. Nearly two-thirds of the addresses represented rural locations. Compared to the rooftop gold standard, E911 locations were more accurate overall than address-matched geocodes (median error 39 and 90 m, respectively). Rural addresses generally had greater error than non-rural addresses, although errors were smaller for E911 locations. For highly prevalent crops within 500 m (>97% of homes), sensitivity was >95% using both data sources; however, lower specificities with address-matched geocodes (more common for rural addresses) led to substantial attenuation of ORs (e.g., corn <500 m ORobs = 1.47 vs. ORtrue = 2.0). Error in the address-matched geocodes resulted in even greater ORobs attenuation for AFO exposures. Errors for North Carolina addresses were generally smaller than those in Iowa. Geocoding error can be minimized when known coordinates are available to test alternative data and methods. Our assessment suggests that where E911 locations are available, they offer an improvement upon address-matched geocodes for rural addresses. Exposure misclassification resulting from positional error is dependent on the geographic database, geocoding method, and the prevalence of exposure.}, number={1}, journal={International Journal of Health Geographics}, publisher={Springer Nature}, author={Jones, Rena R and DellaValle, Curt T and Flory, Abigail R and Nordan, Alex and Hoppin, Jane A and Hofmann, Jonathan N and Chen, Honglei and Giglierano, James and Lynch, Charles F and Beane Freeman, Laura E and et al.}, year={2014}, pages={37} } @article{kitahara_flint_berrington de gonzalez_bernstein_brotzman_macinnis_moore_robien_rosenberg_singh_et al._2014, title={Association between Class III Obesity (BMI of 40–59 kg/m2) and Mortality: A Pooled Analysis of 20 Prospective Studies}, volume={11}, ISSN={1549-1676}, url={http://dx.doi.org/10.1371/journal.pmed.1001673}, DOI={10.1371/journal.pmed.1001673}, abstractNote={In a pooled analysis of 20 prospective studies, Cari Kitahara and colleagues find that class III obesity (BMI of 40–59) is associated with excess rates of total mortality, particularly due to heart disease, cancer, and diabetes. Please see later in the article for the Editors' Summary}, number={7}, journal={PLoS Medicine}, publisher={Public Library of Science (PLoS)}, author={Kitahara, Cari M. and Flint, Alan J. and Berrington de Gonzalez, Amy and Bernstein, Leslie and Brotzman, Michelle and MacInnis, Robert J. and Moore, Steven C. and Robien, Kim and Rosenberg, Philip S. and Singh, Pramil N. and et al.}, editor={Khaw, Kay-TeeEditor}, year={2014}, month={Jul}, pages={e1001673} } @article{kamel_goldman_umbach_chen_richardson_barber_meng_marras_korell_kasten_et al._2014, title={Dietary fat intake, pesticide use, and Parkinson's disease}, volume={20}, ISSN={1353-8020}, url={http://dx.doi.org/10.1016/j.parkreldis.2013.09.023}, DOI={10.1016/j.parkreldis.2013.09.023}, abstractNote={Dietary fat intake may modify Parkinson's disease (PD) risk directly or by altering the response to environmental neurotoxicants including pesticides.We conducted a case-control study of PD nested in the Agricultural Health Study (AHS), a cohort of pesticide applicators and spouses. We evaluated diet and pesticide use before diagnosis in 89 PD cases, confirmed by movement disorder specialists, or a corresponding date in 336 frequency-matched controls. Associations were evaluated using multivariate logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).In the AHS, PD was inversely associated with N-3 polyunsaturated fatty acids (PUFAs) (OR 0.4, 95% CI 0.2-0.8 for highest vs. lowest tertile) and the N-3 precursor α-linolenic acid (0.4, 0.2-0.8). In a meta-analysis of nine studies, including the present one, PD was inversely associated with α-linolenic acid (0.81, 0.68-0.96). In the AHS, associations of PD with the pesticides paraquat and rotenone were modified by fat intake. The OR for paraquat was 4.2 (1.5-12) in individuals with PUFA intake below the median but 1.2 (0.4-3.4) in those with higher intake (p-interaction = 0.10). The OR for rotenone was 5.8 (2.3-15) in those with saturated fat intake above the median but 1.5 (0.5-4.2) in those with lower intake (p-interaction = 0.02).PUFA intake was consistently associated with lower PD risk, and dietary fats modified the association of PD risk with pesticide exposure. If confirmed, these findings suggest that a diet high in PUFAs and low in saturated fats might reduce risk of PD.}, number={1}, journal={Parkinsonism & Related Disorders}, publisher={Elsevier BV}, author={Kamel, Freya and Goldman, Samuel M. and Umbach, David M. and Chen, Honglei and Richardson, Gina and Barber, Marie Richards and Meng, Cheryl and Marras, Connie and Korell, Monica and Kasten, Meike and et al.}, year={2014}, month={Jan}, pages={82–87} } @article{hilton_hoppin_2014, title={Is Helicobacter Pylori an endogenous source of diethyl phthalate in humans?}, volume={134}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2014.08.019}, DOI={10.1016/j.envres.2014.08.019}, abstractNote={Monoethyl phthalate (MEP) is a metabolite used to assess exposure to diethyl phthalate (DEP). Helicobacter Pylori (HP) has been shown to produce DEP in laboratory studies. We used NHANES 1999–2000 data for 1623 adults to investigate whether HP seropositivity was associated with MEP levels. MEP levels were higher in individuals with HP seropositivity (p=0.0237), however the association differed by race. These results suggest that HP may be an endogenous source of DEP in some populations.}, journal={Environmental Research}, publisher={Elsevier BV}, author={Hilton, Gina M. and Hoppin, Jane A.}, year={2014}, month={Oct}, pages={402–404} } @article{weichenthal_villeneuve_burnett_van donkelaar_martin_jones_dellavalle_sandler_ward_hoppin_2014, title={Long-Term Exposure to Fine Particulate Matter: Association with Nonaccidental and Cardiovascular Mortality in the Agricultural Health Study Cohort}, volume={122}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1307277}, DOI={10.1289/ehp.1307277}, abstractNote={Background: Few studies have examined the relationship between long-term exposure to ambient fine particulate matter (PM2.5) and nonaccidental mortality in rural populations.Objective: We examined the relationship between PM2.5 and nonaccidental and cardiovascular mortality in the U.S. Agricultural Health Study cohort.Methods: The cohort (n = 83,378) included farmers, their spouses, and commercial pesticide applicators residing primarily in Iowa and North Carolina. Deaths occurring between enrollment (1993–1997) and 30 December 2009 were identified by record linkage. Six-year average (2001–2006) remote-sensing derived estimates of PM2.5 were assigned to participants' residences at enrollment, and Cox proportional hazards models were used to estimate hazard ratios (HR) in relation to a 10-μg/m3 increase in PM2.5 adjusted for individual-level covariates.Results: In total, 5,931 nonaccidental and 1,967 cardiovascular deaths occurred over a median follow-up time of 13.9 years. PM2.5 was not associated with nonaccidental mortality in the cohort as a whole (HR = 0.95; 95% CI: 0.76, 1.20), but consistent inverse relationships were observed among women. Positive associations were observed between ambient PM2.5 and cardiovascular mortality among men, and these associations were strongest among men who did not move from their enrollment address (HR = 1.63; 95% 0.94, 2.84). In particular, cardiovascular mortality risk in men was significantly increased when analyses were limited to nonmoving participants with the most precise exposure geocoding (HR = 1.87; 95% CI: 1.04, 3.36).Conclusions: Rural PM2.5 may be associated with cardiovascular mortality in men; however, similar associations were not observed among women. Further evaluation is required to explore these sex differences.Citation: Weichenthal S, Villeneuve PJ, Burnett RT, van Donkelaar A, Martin RV, Jones RR, DellaValle CT, Sandler DP, Ward MH, Hoppin JA. 2014. Long-term exposure to fine particulate matter: association with nonaccidental and cardiovascular mortality in the Agricultural Health Study Cohort. Environ Health Perspect 122:609–615; http://dx.doi.org/10.1289/ehp.1307277}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Weichenthal, Scott and Villeneuve, Paul J. and Burnett, Richard T. and van Donkelaar, Aaron and Martin, Randall V. and Jones, Rena R. and DellaValle, Curt T. and Sandler, Dale P. and Ward, Mary H. and Hoppin, Jane A.}, year={2014}, month={Jun}, pages={609–615} } @article{alavanja_hofmann_lynch_hines_barry_barker_buckman_thomas_sandler_hoppin_et al._2014, title={Non-Hodgkin Lymphoma Risk and Insecticide, Fungicide and Fumigant Use in the Agricultural Health Study}, volume={9}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0109332}, DOI={10.1371/journal.pone.0109332}, abstractNote={Farming and pesticide use have previously been linked to non-Hodgkin lymphoma (NHL), chronic lymphocytic leukemia (CLL) and multiple myeloma (MM). We evaluated agricultural use of specific insecticides, fungicides, and fumigants and risk of NHL and NHL-subtypes (including CLL and MM) in a U.S.-based prospective cohort of farmers and commercial pesticide applicators. A total of 523 cases occurred among 54,306 pesticide applicators from enrollment (1993–97) through December 31, 2011 in Iowa, and December 31, 2010 in North Carolina. Information on pesticide use, other agricultural exposures and other factors was obtained from questionnaires at enrollment and at follow-up approximately five years later (1999–2005). Information from questionnaires, monitoring, and the literature were used to create lifetime-days and intensity-weighted lifetime days of pesticide use, taking into account exposure-modifying factors. Poisson and polytomous models were used to calculate relative risks (RR) and 95% confidence intervals (CI) to evaluate associations between 26 pesticides and NHL and five NHL-subtypes, while adjusting for potential confounding factors. For total NHL, statistically significant positive exposure-response trends were seen with lindane and DDT. Terbufos was associated with total NHL in ever/never comparisons only. In subtype analyses, terbufos and DDT were associated with small cell lymphoma/chronic lymphocytic leukemia/marginal cell lymphoma, lindane and diazinon with follicular lymphoma, and permethrin with MM. However, tests of homogeneity did not show significant differences in exposure-response among NHL-subtypes for any pesticide. Because 26 pesticides were evaluated for their association with NHL and its subtypes, some chance finding could have occurred. Our results showed pesticides from different chemical and functional classes were associated with an excess risk of NHL and NHL subtypes, but not all members of any single class of pesticides were associated with an elevated risk of NHL or NHL subtypes. These findings are among the first to suggest links between DDT, lindane, permethrin, diazinon and terbufos with NHL subtypes.}, number={10}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Alavanja, Michael C. R. and Hofmann, Jonathan N. and Lynch, Charles F. and Hines, Cynthia J. and Barry, Kathryn H. and Barker, Joseph and Buckman, Dennis W. and Thomas, Kent and Sandler, Dale P. and Hoppin, Jane A. and et al.}, editor={Akiba, SuminoriEditor}, year={2014}, month={Oct}, pages={e109332} } @article{weichenthal_hoppin_reeves_2014, title={Obesity and the cardiovascular health effects of fine particulate air pollution}, volume={22}, ISSN={1930-7381}, url={http://dx.doi.org/10.1002/oby.20748}, DOI={10.1002/oby.20748}, abstractNote={This review examines evidence related to the potential impact of obesity on the cardiovascular health effects of fine particulate air pollution (PM₂.₅).A PubMed search was conducted in December, 2013 and studies were included if they examined the relationship between PM₂.₅ and cardiovascular health as well as effect modification by obesity.One hundred twenty-one citations were reviewed; three large prospective cohort studies and 14 panel studies with short-term follow-up met the above criteria. All three cohort studies reported stronger associations between PM₂.₅ and cardiovascular mortality among obese subjects and one reported a significant trend of increased risk with increased body mass index. Similarly, 11 of 14 panel studies reported stronger associations between PM₂.₅ and acute changes in physiological measures of cardiovascular health among obese subjects including outcomes such as blood pressure and arrhythmia. Although interactions were not always statistically significant, the consistent pattern of stronger associations among obese subjects suggests that obesity may modify the impact of PM2.5 on cardiovascular health.Epidemiological evidence suggests that obesity may increase susceptibility to the cardiovascular health effects of PM₂.₅. This an important area of research as the public health impacts of air pollution could increase with increasing prevalence of obesity.}, number={7}, journal={Obesity}, publisher={Wiley}, author={Weichenthal, Scott and Hoppin, Jane A. and Reeves, Francois}, year={2014}, month={Mar}, pages={1580–1589} } @article{goldman_kamel_ross_jewell_marras_hoppin_umbach_bhudhikanok_meng_korell_et al._2014, title={Peptidoglycan recognition protein genes and risk of Parkinson's disease}, volume={29}, ISSN={0885-3185}, url={http://dx.doi.org/10.1002/mds.25895}, DOI={10.1002/mds.25895}, abstractNote={ABSTRACT Increased gut permeability, inflammation, and colonic α‐synuclein pathology are present in early Parkinson's disease (PD) and have been proposed to contribute to PD pathogenesis. Peptidoglycan is a structural component of the bacterial cell wall. Peptidoglycan recognition proteins (PGRPs) maintain healthy gut microbial flora by regulating the immune response to both commensal and harmful bacteria. We tested the hypothesis that variants in genes that encode PGRPs are associated with PD risk. Participants in two independent case‐control studies were genotyped for 30 single‐nucleotide polymorphisms (SNPs) in the four PGLYRP genes. Using logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) adjusted for potential confounding variables, we conducted analyses in each study, separately and pooled. One SNP failed the assay, and three had little to no variation. The ORs were similar in both study populations. In pooled analyses, three of seven PGLYRP2 SNPs (rs3813135, rs733731, rs892145), one of five PGLYRP3 SNPs (rs2987763), and six of nine PGLYRP4 SNPs (rs10888557, rs12063091, rs3006440, rs3006448, rs3006458, and rs3014864) were significantly associated with PD risk. Association was strongest for PGLYRP4 5'untranslated region (UTR) SNP rs10888557 (GG reference, CG OR 0.6 [95%CI 0.4‐0.9], CC OR 0.15 [95%CI 0.04‐0.6]; log‐additive P ‐trend, 0.0004). Common variants in PGLYRP genes are associated with PD risk in two independent studies. These results require replication, but they are consistent with hypotheses of a causative role for the gut microbiota and gastrointestinal immune response in PD. © 2014 International Parkinson and Movement Disorder Society}, number={9}, journal={Movement Disorders}, publisher={Wiley}, author={Goldman, Samuel M. and Kamel, Freya and Ross, G. Webster and Jewell, Sarah A. and Marras, Connie and Hoppin, Jane A. and Umbach, David M. and Bhudhikanok, Grace S. and Meng, Cheryl and Korell, Monica and et al.}, year={2014}, month={May}, pages={1171–1180} } @article{starling_engel_richardson_baird_haug_stuebe_klungsoyr_harmon_becher_thomsen_et al._2014, title={Perfluoroalkyl Substances During Pregnancy and Validated Preeclampsia Among Nulliparous Women in the Norwegian Mother and Child Cohort Study}, volume={179}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwt432}, DOI={10.1093/aje/kwt432}, abstractNote={Perfluoroalkyl substances (PFAS) are persistent and ubiquitous environmental contaminants, and human exposure to these substances may be related to preeclampsia, a common pregnancy complication. Previous studies have found serum concentrations of PFAS to be positively associated with pregnancy-induced hypertension and preeclampsia in a population with high levels of exposure to perfluorooctanoate. Whether this association exists among pregnant women with background levels of PFAS exposure is unknown. Using data from the Norwegian Mother and Child Cohort Study conducted by the Norwegian Institute of Public Health, we carried out a study of nulliparous pregnant women enrolled in 2003–2007 (466 cases, 510 noncases) to estimate associations between PFAS concentrations and an independently validated diagnosis of preeclampsia. We measured levels of 9 PFAS in maternal plasma extracted midpregnancy; statistical analyses were restricted to 7 PFAS that were quantifiable in more than 50% of samples. In proportional hazards models adjusted for maternal age, prepregnancy body mass index (weight (kg)/height (m)2), educational level, and smoking status, we observed no strongly positive associations between PFAS levels and preeclampsia. We found an inverse association between preeclampsia and the highest quartile of perfluoroundecanoic acid concentration relative to the lowest quartile (hazard ratio = 0.55, 95% confidence interval: 0.38, 0.81). Overall, our findings do not support an increased risk of preeclampsia among nulliparous Norwegian women with background levels of PFAS exposure.}, number={7}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Starling, A. P. and Engel, S. M. and Richardson, D. B. and Baird, D. D. and Haug, L. S. and Stuebe, A. M. and Klungsoyr, K. and Harmon, Q. and Becher, G. and Thomsen, C. and et al.}, year={2014}, month={Feb}, pages={824–833} } @article{starling_engel_whitworth_richardson_stuebe_daniels_haug_eggesbø_becher_sabaredzovic_et al._2014, title={Perfluoroalkyl substances and lipid concentrations in plasma during pregnancy among women in the Norwegian Mother and Child Cohort Study}, volume={62}, ISSN={0160-4120}, url={http://dx.doi.org/10.1016/j.envint.2013.10.004}, DOI={10.1016/j.envint.2013.10.004}, abstractNote={Perfluoroalkyl substances (PFASs) are widespread and persistent environmental pollutants. Previous studies, primarily among non-pregnant individuals, suggest positive associations between PFAS levels and certain blood lipids. If there is a causal link between PFAS concentrations and elevated lipids during pregnancy, this may suggest a mechanism by which PFAS exposure leads to certain adverse pregnancy outcomes, including preeclampsia. This cross-sectional analysis included 891 pregnant women enrolled in the Norwegian Mother and Child (MoBa) Cohort Study in 2003–2004. Non-fasting plasma samples were obtained at mid-pregnancy and analyzed for nineteen PFASs. Total cholesterol, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein cholesterol, and triglycerides were measured in plasma. Linear regression was used to quantify associations between each PFAS exposure and each lipid outcome. A multiple PFAS model was also fitted. Seven PFASs were quantifiable in > 50% of samples. Perfluorooctane sulfonate (PFOS) concentration was associated with total cholesterol, which increased 4.2 mg/dL per inter-quartile shift (95% CI = 0.8, 7.7) in adjusted models. Five of the seven PFASs studied were positively associated with HDL cholesterol, and all seven had elevated HDL associated with the highest quartile of exposure. Perfluoroundecanoic acid showed the strongest association with HDL: HDL increased 3.7 mg/dL per inter-quartile shift (95% CI = 2.5, 4.9). Plasma concentrations of PFASs were positively associated with HDL cholesterol, and PFOS was positively associated with total cholesterol in this sample of pregnant Norwegian women. While elevated HDL is not an adverse outcome per se, elevated total cholesterol associated with PFASs during pregnancy could be of concern if causal.}, journal={Environment International}, publisher={Elsevier BV}, author={Starling, Anne P. and Engel, Stephanie M. and Whitworth, Kristina W. and Richardson, David B. and Stuebe, Alison M. and Daniels, Julie L. and Haug, Line Småstuen and Eggesbø, Merete and Becher, Georg and Sabaredzovic, Azemira and et al.}, year={2014}, month={Jan}, pages={104–112} } @article{beard_umbach_hoppin_richards_alavanja_blair_sandler_kamel_2014, title={Pesticide Exposure and Depression among Male Private Pesticide Applicators in the Agricultural Health Study}, volume={122}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1307450}, DOI={10.1289/ehp.1307450}, abstractNote={Background: Pesticide exposure may be positively associated with depression. Few previous studies have considered the episodic nature of depression or examined individual pesticides.Objective: We evaluated associations between pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study.Methods: We analyzed data for 10 pesticide classes and 50 specific pesticides used by 21,208 applicators enrolled in 1993–1997 who completed a follow-up telephone interview in 2005–2010. We divided applicators who reported a physician diagnosis of depression (n = 1,702; 8%) into those who reported a previous diagnosis of depression at enrollment but not follow-up (n = 474; 28%), at both enrollment and follow-up (n = 540; 32%), and at follow-up but not enrollment (n = 688; 40%) and used polytomous logistic regression to estimate odds ratios (ORs) and 95% CIs. We used inverse probability weighting to adjust for potential confounders and to account for the exclusion of 3,315 applicators with missing covariate data and 24,619 who did not complete the follow-up interview.Results: After weighting for potential confounders, missing covariate data, and dropout, ever-use of two pesticide classes, fumigants and organochlorine insecticides, and seven individual pesticides—the fumigants aluminum phosphide and ethylene dibromide; the phenoxy herbicide (2,4,5-trichlorophenoxy)acetic acid (2,4,5-T); the organochlorine insecticide dieldrin; and the organophosphate insecticides diazinon, malathion, and parathion—were all positively associated with depression in each case group, with ORs between 1.1 and 1.9.Conclusions: Our study supports a positive association between pesticide exposure and depression, including associations with several specific pesticides.Citation: Beard JD, Umbach DM, Hoppin JA, Richards M, Alavanja MCR, Blair A, Sandler DP, Kamel F. 2014. Pesticide exposure and depression among male private pesticide applicators in the Agricultural Health Study. Environ Health Perspect 122:984–991; http://dx.doi.org/10.1289/ehp.1307450}, number={9}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Beard, John D. and Umbach, David M. and Hoppin, Jane A. and Richards, Marie and Alavanja, Michael C.R. and Blair, Aaron and Sandler, Dale P. and Kamel, Freya}, year={2014}, month={Sep}, pages={984–991} } @article{starling_umbach_kamel_long_sandler_hoppin_2014, title={Pesticide use and incident diabetes among wives of farmers in the Agricultural Health Study}, volume={71}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2013-101659}, DOI={10.1136/oemed-2013-101659}, abstractNote={

Objective

To estimate associations between use of specific agricultural pesticides and incident diabetes in women.

Methods

We used data from the Agricultural Health Study, a large prospective cohort of pesticide applicators and their spouses in Iowa and North Carolina. For comparability with previous studies of farmers, we limited analysis to 13 637 farmers’ wives who reported ever personally mixing or applying pesticides at enrolment (1993–1997), who provided complete data on required covariates and diabetes diagnosis and who reported no previous diagnosis of diabetes at enrolment. Participants reported ever-use of 50 specific pesticides at enrolment and incident diabetes at one of two follow-up interviews within an average of 12 years of enrolment. We fit Cox proportional hazards models with age as the time scale and adjusting for state and body mass index to estimate HRs and 95% CIs for each of the 45 pesticides with sufficient users.

Results

Five pesticides were positively associated with incident diabetes (n=688; 5%): three organophosphates, fonofos (HR=1.56, 95% CI 1.11 to 2.19), phorate (HR=1.57, 95% CI 1.14 to 2.16) and parathion (HR=1.61, 95% CI 1.05 to 2.46); the organochlorine dieldrin (HR=1.99, 95% CI 1.12 to 3.54); and the herbicide 2,4,5-T/2,4,5-TP (HR=1.59, 95% CI 1.00 to 2.51). With phorate and fonofos together in one model to account for their correlation, risks for both remained elevated, though attenuated compared with separate models.

Conclusions

Results are consistent with previous studies reporting an association between specific organochlorines and diabetes and add to growing evidence that certain organophosphates also may increase risk.}, number={9}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Starling, Anne P and Umbach, David M and Kamel, Freya and Long, Stuart and Sandler, Dale P and Hoppin, Jane A}, year={2014}, month={Apr}, pages={629–635} } @article{salo_arbes_jaramillo_calatroni_weir_sever_hoppin_rose_liu_gergen_et al._2014, title={Prevalence of allergic sensitization in the United States: Results from the National Health and Nutrition Examination Survey (NHANES) 2005-2006}, volume={134}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2013.12.1071}, DOI={10.1016/j.jaci.2013.12.1071}, abstractNote={Allergic sensitization is an important risk factor for the development of atopic disease. The National Health and Nutrition Examination Survey (NHANES) 2005-2006 provides the most comprehensive information on IgE-mediated sensitization in the general US population.We investigated clustering, sociodemographic, and regional patterns of allergic sensitization and examined risk factors associated with IgE-mediated sensitization.Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Participants aged 1 year or older (n = 9440) were tested for serum specific IgEs (sIgEs) to inhalant and food allergens; participants 6 years or older were tested for 19 sIgEs, and children aged 1 to 5 years were tested for 9 sIgEs. Serum samples were analyzed by using the ImmunoCAP System. Information on demographics and participants' characteristics was collected by means of questionnaire.Of the study population aged 6 years and older, 44.6% had detectable sIgEs, whereas 36.2% of children aged 1 to 5 years were sensitized to 1 or more allergens. Allergen-specific IgEs clustered into 7 groups that might have largely reflected biological cross-reactivity. Although sensitization to individual allergens and allergen types showed regional variation, the overall prevalence of sensitization did not differ across census regions, except in early childhood. In multivariate modeling young age, male sex, non-Hispanic black race/ethnicity, geographic location (census region), and reported pet avoidance measures were most consistently associated with IgE-mediated sensitization.The overall prevalence of allergic sensitization does not vary across US census regions, except in early life, although allergen-specific sensitization differs based on sociodemographic and regional factors. Biological cross-reactivity might be an important but not the sole contributor to the clustering of allergen-specific IgEs.}, number={2}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Salo, Päivi M. and Arbes, Samuel J., Jr. and Jaramillo, Renee and Calatroni, Agustin and Weir, Charles H. and Sever, Michelle L. and Hoppin, Jane A. and Rose, Kathryn M. and Liu, Andrew H. and Gergen, Peter J. and et al.}, year={2014}, month={Aug}, pages={350–359} } @article{bertelsen_engel_jusko_calafat_hoppin_london_eggesbø_aase_zeiner_reichborn-kjennerud_et al._2014, title={Reliability of triclosan measures in repeated urine samples from Norwegian pregnant women}, volume={24}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2013.95}, DOI={10.1038/jes.2013.95}, abstractNote={Triclosan (TCS) is a synthetic antibacterial chemical that is used in personal care products and is measurable in urine. Urinary TCS has been associated with allergy in children in Norway and the United States. A reasonable degree of temporal reliability of TCS urinary concentrations has been reported among US children as well as for Puerto Rican pregnant women. We examined the reliability of TCS measures in urine among Norwegian pregnant women. TCS was measured in spot urine samples collected in gestational weeks 17, 23, and 29 from 45 women in The Norwegian Mother and Child Cohort Study (MoBa) enrolled in 2007 and 2008. Spearman’s rank correlation coefficient (rs) and intraclass correlation coefficient (ICC) statistics were calculated. Fifty-six percent of the 45 women had a least one sample with a value above the method limit of detection (2.3 μg/l). The correlation coefficients were 0.61 for TCS concentrations at 17 and 23 weeks and 0.49 for concentrations at 17 and 29 weeks. For the three time points, the ICC was 0.49. The reliability of TCS concentrations in repeated urine samples from pregnant Norwegian women was reasonably good, suggesting a single urine sample can adequately represent TCS exposure during pregnancy.}, number={5}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Bertelsen, Randi J and Engel, Stephanie M and Jusko, Todd A and Calafat, Antonia M and Hoppin, Jane A and London, Stephanie J and Eggesbø, Merete and Aase, Heidi and Zeiner, Pål and Reichborn-Kjennerud, Ted and et al.}, year={2014}, month={Jan}, pages={517–521} } @article{hoppin_umbach_long_rinsky_henneberger_salo_zeldin_london_alavanja_blair_et al._2014, title={Respiratory disease in United States farmers}, volume={71}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2013-101983}, DOI={10.1136/oemed-2013-101983}, abstractNote={

Objectives

Farmers may be at increased risk for adverse respiratory outcomes compared with the general population due to their regular exposures to dusts, animals and chemicals. However, early life farm exposures to microbial agents may result in reduced risk. Understanding respiratory disease risk among farmers and identifying differences between farmers and other populations may lead to better understanding of the contribution of environmental exposures to respiratory disease risk in the general population.

Methods

We compared the prevalence of self-reported respiratory outcomes in 43548 participants from the Agricultural Health Study (AHS), a prospective cohort of farmers and their spouses from Iowa and North Carolina, with data from adult participants in the National Health and Nutrition Examination Survey (NHANES) over the same period (2005–2010).

Results

AHS participants had lower prevalences of respiratory diseases (asthma, adult-onset asthma, chronic bronchitis and emphysema), but higher prevalences of current respiratory symptoms (wheeze, cough and phlegm) even after controlling for smoking, body mass index and population characteristics. The overall prevalence of asthma in the AHS (7.2%, 95% CI 6.9 to 7.4) was 52% of that in NHANES (13.8%, 95% CI 13.3 to 14.3), although the prevalence of adult-onset asthma among men did not differ (3.6% for AHS, 3.7% for NHANES). Conversely, many respiratory symptoms were more common in the AHS than NHANES, particularly among men.

Conclusions

These findings suggest that farmers and their spouses have lower risk for adult-onset respiratory diseases compared with the general population, and potentially higher respiratory irritation as evidenced by increased respiratory symptoms.}, number={7}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Hoppin, Jane A and Umbach, David M and Long, Stuart and Rinsky, Jessica L and Henneberger, Paul K and Salo, Paivi M and Zeldin, Darryl C and London, Stephanie J and Alavanja, Michael C R and Blair, Aaron and et al.}, year={2014}, month={Jun}, pages={484–491} } @article{jack_motsinger-reif_koutros_alavanja_beane freeman_hoppin_2014, title={Single-Nucleotide Polymorphism Data Support the General Unrelatedness of the Males in the Agricultural Health Study}, volume={23}, ISSN={1055-9965 1538-7755}, url={http://dx.doi.org/10.1158/1055-9965.EPI-14-0276}, DOI={10.1158/1055-9965.epi-14-0276}, abstractNote={Farming is often a family and multigenerational business. Relatedness among farmers could bias gene-environment interaction analysis. To evaluate the potential relatedness of farmers, we used data from a nested case-control study of prostate cancer conducted in the Agricultural Health Study (AHS), a prospective study of farmers in Iowa and North Carolina.We analyzed the genetic data for 25,009 SNPs (single-nucleotide polymorphisms) from 2,220 White participants to test for cryptic relatedness among these farmers. We used two software packages: (i) PLINK, to calculate inbreeding coefficients and identity-by-descent (IBD) statistics and (ii) EIGENSOFT, to perform a principal component analysis on the genetic data.Inbreeding coefficients estimates and IBD statistics show that the subjects are overwhelmingly unrelated, with little potential for cryptic relatedness in these data.Our analysis rejects the hypothesis that individuals in the case-control study exhibit cryptic relatedness.These findings are important for all subsequent analyses of gene-environment interactions in the AHS.}, number={10}, journal={Cancer Epidemiology Biomarkers & Prevention}, publisher={American Association for Cancer Research (AACR)}, author={Jack, J. R. and Motsinger-Reif, A. A. and Koutros, S. and Alavanja, M. C. and Beane Freeman, L. E. and Hoppin, J. A.}, year={2014}, month={Jul}, pages={2192–2195} } @article{sofer_schifano_hoppin_hou_baccarelli_2013, title={A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure}, volume={29}, ISSN={1460-2059 1367-4803}, url={http://dx.doi.org/10.1093/bioinformatics/btt498}, DOI={10.1093/bioinformatics/btt498}, abstractNote={Abstract Motivation: DNA methylation is a heritable modifiable chemical process that affects gene transcription and is associated with other molecular markers (e.g. gene expression) and biomarkers (e.g. cancer or other diseases). Current technology measures methylation in hundred of thousands, or millions of CpG sites throughout the genome. It is evident that neighboring CpG sites are often highly correlated with each other, and current literature suggests that clusters of adjacent CpG sites are co-regulated. Results: We develop the Adjacent Site Clustering (A-clustering) algorithm to detect sets of neighboring CpG sites that are correlated with each other. To detect methylation regions associated with exposure, we propose an analysis pipeline for high-dimensional methylation data in which CpG sites within regions identified by A-clustering are modeled as multivariate responses to environmental exposure using a generalized estimating equation approach that assumes exposure equally affects all sites in the cluster. We develop a correlation preserving simulation scheme, and study the proposed methodology via simulations. We study the clusters detected by the algorithm on high dimensional dataset of peripheral blood methylation of pesticide applicators. Availability: We provide the R package Aclust that efficiently implements the A-clustering and the analysis pipeline, and produces analysis reports. The package is found on http://www.hsph.harvard.edu/tamar-sofer/packages/ Contact: tsofer@hsph.harvard.edu Supplementary information: Supplementary data are available at Bioinformatics online.}, number={22}, journal={Bioinformatics}, publisher={Oxford University Press (OUP)}, author={Sofer, Tamar and Schifano, Elizabeth D. and Hoppin, Jane A. and Hou, Lifang and Baccarelli, Andrea A.}, year={2013}, month={Aug}, pages={2884–2891} } @article{rinsky_hoppin_blair_he_beane freeman_chen_2013, title={Agricultural Exposures and Stroke Mortality in the Agricultural Health Study}, volume={76}, ISSN={1528-7394 1087-2620}, url={http://dx.doi.org/10.1080/15287394.2013.819308}, DOI={10.1080/15287394.2013.819308}, abstractNote={Exposures associated with common agricultural activities may increase risk of stroke. The authors evaluated associations between self-reported agricultural activities including pesticide use and handling of crops and stroke mortality among 51,603 male pesticide applicators enrolled in the Agricultural Health Study (AHS). Vital status was obtained through 2008. Stroke mortality was defined by underlying or contributing cause of death (ICD-9 430–438, ICD-10 I60–I69). Information regarding lifetime pesticide use, working with crops or animals, engagement in other agricultural activities, and potential confounders was self-reported at enrollment. Cox proportional hazards models, with age as the time scale, were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) adjusted for state of residence, smoking status, and alcohol consumption. Median follow-up time was 13 yr, during which 308 stroke deaths occurred. No measure of overall or specific pesticide use was positively associated with mortality due to stroke. Stroke mortality was inversely associated with handling hay, grain, or silage at least once each year as reported at enrollment (HR: 0.75; 95% CI: 0.58, 0.98). There was no evidence of an association between pesticide use and stroke mortality. The inverse association between handling of hays and grains and stroke mortality may be due to (1) those engaging in such activities being healthier than those who did not or (2) exposure to some biological agent present in hays and grains. Further investigation of incident stroke, rather than stroke mortality, as well as stroke subtypes, is needed to determine the full role of agricultural exposures and stroke.}, number={13}, journal={Journal of Toxicology and Environmental Health, Part A}, publisher={Informa UK Limited}, author={Rinsky, Jessica L. and Hoppin, Jane A. and Blair, Aaron and He, Ka and Beane Freeman, Laura E. and Chen, Honglei}, year={2013}, month={Jul}, pages={798–814} } @article{kim_mason_nelson_afton_essader_medlin_levine_hoppin_lin_knowler_et al._2013, title={Arsenic Exposure and Incidence of Type 2 Diabetes in Southwestern American Indians}, volume={177}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kws329}, DOI={10.1093/aje/kws329}, abstractNote={Association of urinary arsenic concentration with incident diabetes was examined in American Indians from Arizona who have a high prevalence of type 2 diabetes and were screened for diabetes between 1982 and 2007. The population resides where drinking water contains arsenic at concentrations above federally recommended limits. A total of 150 nondiabetic subjects aged ≥25 years who subsequently developed type 2 diabetes were matched by year of examination and sex to 150 controls who remained nondiabetic for ≥10 years. Total urinary arsenic concentration, adjusted for urinary creatinine level, ranged from 6.6 µg/L to 123.1 µg/L, and inorganic arsenic concentration ranged from 0.1 µg/L to 36.0 µg/L. In logistic regression models adjusted for age, sex, body mass index, and urinary creatinine level, the odds ratios for incident diabetes were 1.11 (95% confidence interval (CI): 0.79, 1.57) and 1.16 (95% CI: 0.89, 1.53) for a 2-fold increase in total arsenic and inorganic arsenic, respectively. Categorical analyses suggested a positive relationship between quartiles of inorganic arsenic and incident diabetes (P = 0.056); post-hoc comparison of quartiles 2–4 with quartile 1 revealed 2-fold higher odds of diabetes in the upper quartiles (OR = 2.14, 95% CI: 1.19, 3.85). Modestly elevated exposure to inorganic arsenic may predict type 2 diabetes in American Indians. Larger studies that include measures of speciated arsenic are required for confirmation.}, number={9}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Kim, N. H. and Mason, C. C. and Nelson, R. G. and Afton, S. E. and Essader, A. S. and Medlin, J. E. and Levine, K. E. and Hoppin, J. A. and Lin, C. and Knowler, W. C. and et al.}, year={2013}, month={Mar}, pages={962–969} } @article{wang_starling_haug_eggesbo_becher_thomsen_travlos_king_hoppin_rogan_et al._2013, title={Association between Perfluoroalkyl substances and thyroid stimulating hormone among pregnant women: a cross-sectional study}, volume={12}, ISSN={1476-069X}, url={http://dx.doi.org/10.1186/1476-069X-12-76}, DOI={10.1186/1476-069X-12-76}, abstractNote={Perfluoroalkyl substances (PFASs) are a group of highly persistent chemicals that are widespread contaminants in wildlife and humans. Exposure to PFAS affects thyroid homeostasis in experimental animals and possibly in humans. The objective of this study was to examine the association between plasma concentrations of PFASs and thyroid stimulating hormone (TSH) among pregnant women.A total of 903 pregnant women who enrolled in the Norwegian Mother and Child Cohort Study from 2003 to 2004 were studied. Concentrations of thirteen PFASs and TSH were measured in plasma samples collected around the 18th week of gestation. Linear regression models were used to evaluate associations between PFASs and TSH.Among the thirteen PFASs, seven were detected in more than 60% of samples and perfluorooctane sulfonate (PFOS) had the highest concentrations (median, 12.8 ng/mL; inter-quartile range [IQR], 10.1 -16.5 ng/mL). The median TSH concentration was 3.5 (IQR, 2.4 - 4.8) μIU/mL. Pregnant women with higher PFOS had higher TSH levels. After adjustment, with each 1 ng/mL increase in PFOS concentration, there was a 0.8% (95% confidence interval: 0.1%, 1.6%) rise in TSH. The odds ratio of having an abnormally high TSH, however, was not increased, and other PFASs were unrelated to TSH.Our results suggest an association between PFOS and TSH in pregnant women that is small and may be of no clinical significance.}, number={1}, journal={Environmental Health}, publisher={Springer Nature}, author={Wang, Yan and Starling, Anne P and Haug, Line S and Eggesbo, Merete and Becher, Georg and Thomsen, Cathrine and Travlos, Gregory and King, Debra and Hoppin, Jane A and Rogan, Walter J and et al.}, year={2013}, month={Sep} } @article{brantsæter_whitworth_ydersbond_haug_haugen_knutsen_thomsen_meltzer_becher_sabaredzovic_et al._2013, title={Determinants of plasma concentrations of perfluoroalkyl substances in pregnant Norwegian women}, volume={54}, ISSN={0160-4120}, url={http://dx.doi.org/10.1016/j.envint.2012.12.014}, DOI={10.1016/j.envint.2012.12.014}, abstractNote={Perfluoroalkyl substances (PFASs) are widespread pollutants that have been associated with adverse health effects although not on a consistent basis. Diet has been considered the main source of exposure. The aim of the present study was to identify determinants of four plasma PFASs in pregnant Norwegian women. This study is based in the Norwegian Mother and Child Cohort Study (MoBa) conducted by the Norwegian Institute of Public Health. Our sample included 487 women who enrolled in MoBa from 2003 to 2004. A questionnaire regarding sociodemographic, medical, and reproductive history was completed at 17 weeks of gestation and a dietary questionnaire was completed at 22 weeks of gestation. Maternal plasma samples were obtained around 17 weeks of gestation. Plasma concentrations of four PFASs (perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), perfluorohexane sulfonate (PFHxS), and perfluorononanoate (PFNA)) were examined in relation to demographic, lifestyle, dietary, and pregnancy-related covariates. Predictors were identified by optimizing multiple linear regression models using Akaike's information criterion (AIC). Parity was the determinant with the largest influence on plasma PFAS concentrations, with r2 between 0.09 and 0.32 in simple regression models. In optimal multivariate models, when compared to nulliparous women, parous women had 46%, 70%, 19%, and 62% lower concentrations of PFOS, PFOA, PFHxS, and PFNA respectively (p < 0.001 except for PFHxS, p < 0.01). In all these models, duration of breastfeeding was associated with reduced PFAS levels. PFOA showed the largest reduction from breastfeeding, with a 2–3% reduction per month of breastfeeding in typical cases. Levels of PFOS, PFOA, and PFNA increased with time since most recent pregnancy. While pregnancy-related factors were the most important predictors, diet was a significant factor explaining up to 4% of the variance. One quartile increase in estimated dietary PFAS intake was associated with plasma PFOS, PFOA, PFHxS, and PFNA concentration increases of 7.2%, 3.3%, 5.8% and 9.8%, respectively, resulting in small, although non-trivial absolute changes in PFAS concentrations. Previous pregnancies and breastfeeding duration were the most important determinants of PFASs in this sample of pregnant women.}, journal={Environment International}, publisher={Elsevier BV}, author={Brantsæter, A.L. and Whitworth, K.W. and Ydersbond, T.A. and Haug, L.S. and Haugen, M. and Knutsen, H.K. and Thomsen, C. and Meltzer, H.M. and Becher, G. and Sabaredzovic, A. and et al.}, year={2013}, month={Apr}, pages={74–84} } @article{henneberger_liang_london_umbach_sandler_hoppin_2013, title={Exacerbation of symptoms in agricultural pesticide applicators with asthma}, volume={87}, ISSN={0340-0131 1432-1246}, url={http://dx.doi.org/10.1007/s00420-013-0881-x}, DOI={10.1007/s00420-013-0881-x}, abstractNote={Exacerbation is a critical event in asthma management. We investigated whether exacerbation of symptoms is associated with farming exposures among agricultural pesticide applicators with asthma. Participants were pesticide applicators with active asthma (wheezing and breathing problems in past 12 months) who completed enrollment questionnaires for the Agricultural Health Study (AHS). Exacerbation of asthma was defined as having visited a hospital emergency room or doctor for an episode of wheezing or whistling in the past 12 months. Exposures of interest were using 36 specific pesticides in the past 12 months and conducting various agricultural activities. Adjusted odds ratios (ORs) were estimated by logistic regression while controlling for potential confounders. The 926 AHS adult pesticide applicators with active asthma included 202 (22 %) with exacerbation. Inverse associations with exacerbation were observed for two herbicides [glyphosate, odds ratio (OR) = 0.5, 95 % confidence interval (CI) 0.3, 0.8, and paraquat, OR = 0.3, 95 % CI 0.1, 0.9] and several agricultural activities (repairing engines, grinding metal, driving diesel tractors, and performing veterinary procedures). Only asthma cases with allergies (i.e., doctor-diagnosed hay fever or eczema, 46 %) had positive exacerbation–pesticide associations, with OR = 2.1 (95 % CI 1.1, 4.1) for the herbicide pendimethalin and OR = 10.2 (95 % CI 1.9, 55) for the insecticide aldicarb. The inverse associations with two pesticides and specific farm activities are consistent with the possibility that asthma cases prone to exacerbation may avoid exposures that trigger symptoms. Although limited by small sample size and a cross-sectional design, our study suggests that use of specific pesticides may contribute to exacerbation of asthma among individuals with allergies.}, number={4}, journal={International Archives of Occupational and Environmental Health}, publisher={Springer Science and Business Media LLC}, author={Henneberger, Paul K. and Liang, Xiaoming and London, Stephanie J. and Umbach, David M. and Sandler, Dale P. and Hoppin, Jane A.}, year={2013}, month={May}, pages={423–432} } @article{koutros_berndt_hughes barry_andreotti_hoppin_sandler_yeager_burdett_yuenger_alavanja_et al._2013, title={Genetic Susceptibility Loci, Pesticide Exposure and Prostate Cancer Risk}, volume={8}, ISSN={1932-6203}, url={http://dx.doi.org/10.1371/journal.pone.0058195}, DOI={10.1371/journal.pone.0058195}, abstractNote={Uncovering SNP (single nucleotide polymorphisms)-environment interactions can generate new hypotheses about the function of poorly characterized genetic variants and environmental factors, like pesticides. We evaluated SNP-environment interactions between 30 confirmed prostate cancer susceptibility loci and 45 pesticides and prostate cancer risk in 776 cases and 1,444 controls in the Agricultural Health Study. We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test. After correction for multiple tests using the False Discovery Rate method, two interactions remained noteworthy. Among men carrying two T alleles at rs2710647 in EH domain binding protein 1 (EHBP1) SNP, the risk of prostate cancer in those with high malathion use was 3.43 times those with no use (95% CI: 1.44–8.15) (P-interaction = 0.003). Among men carrying two A alleles at rs7679673 in TET2, the risk of prostate cancer associated with high aldrin use was 3.67 times those with no use (95% CI: 1.43, 9.41) (P-interaction = 0.006). In contrast, associations were null for other genotypes. Although additional studies are needed and the exact mechanisms are unknown, this study suggests known genetic susceptibility loci may modify the risk between pesticide use and prostate cancer.}, number={4}, journal={PLoS ONE}, publisher={Public Library of Science (PLoS)}, author={Koutros, Stella and Berndt, Sonja I. and Hughes Barry, Kathryn and Andreotti, Gabriella and Hoppin, Jane A. and Sandler, Dale P. and Yeager, Meredith and Burdett, Laurie A. and Yuenger, Jeffrey and Alavanja, Michael C. R. and et al.}, editor={Scheurer, MichaelEditor}, year={2013}, month={Apr}, pages={e58195} } @article{goldner_sandler_yu_shostrom_hoppin_kamel_levan_2013, title={Hypothyroidism and Pesticide Use Among Male Private Pesticide Applicators in the Agricultural Health Study}, volume={55}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e31829b290b}, DOI={10.1097/JOM.0b013e31829b290b}, abstractNote={Objective: Evaluate the association between thyroid disease and use of insecticides, herbicides, and fumigants/fungicides in male applicators in the Agricultural Health Study. Methods: We examined the association between use of 50 specific pesticides and self-reported hypothyroidism, hyperthyroidism, and "other" thyroid disease among 22,246 male pesticide applicators. Results: There was increased odds of hypothyroidism with ever use of the herbicides 2,4-D (2,4-dichlorophenoxyacetic acid), 2,4,5-T (2,4,5-trichlorophenoxyacetic acid), 2,4,5-TP (2,4,5-trichlorophenoxy-propionic acid), alachlor, dicamba, and petroleum oil. Hypothyroidism was also associated with ever use of eight insecticides: organochlorines chlordane, dichlorodiphenyltrichloroethane (DDT), heptachlor, lindane, and toxaphene; organophosphates diazinon and malathion; and the carbamate carbofuran. Exposure–response analysis showed increasing odds with increasing level of exposure for the herbicides alachlor and 2,4-D and the insecticides aldrin, chlordane, DDT, lindane, and parathion. Conclusion: There is an association between hypothyroidism and specific herbicides and insecticides in male applicators, similar to previous results for spouses.}, number={10}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Goldner, Whitney S. and Sandler, Dale P. and Yu, Fang and Shostrom, Valerie and Hoppin, Jane A. and Kamel, Freya and LeVan, Tricia D.}, year={2013}, month={Oct}, pages={1171–1178} } @article{safaeian_rajaraman_hartge_yeager_linet_butler_ruder_purdue_hsing_beane-freeman_et al._2013, title={Joint effects between five identified risk variants, allergy, and autoimmune conditions on glioma risk}, volume={24}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-013-0244-7}, DOI={10.1007/s10552-013-0244-7}, abstractNote={Common variants in two of the five genetic regions recently identified from genome-wide association studies (GWAS) of risk of glioma were reported to interact with a history of allergic symptoms. In a pooled analysis of five epidemiologic studies, we evaluated the association between the five GWAS implicated gene variants and allergies and autoimmune conditions (AIC) on glioma risk (851 adult glioma cases and 3,977 controls). We further evaluated the joint effects between allergies and AIC and these gene variants on glioma risk. Risk estimates were calculated as odds ratios (OR) and 95 % confidence intervals (95 % CI), adjusted for age, gender, and study. Joint effects were evaluated by conducting stratified analyses whereby the risk associations (OR and 95 % CI) with the allergy or autoimmune conditions for glioma were evaluated by the presence or absence of the ‘at-risk’ variant, and estimated p interaction by fitting models with the main effects of allergy or autoimmune conditions and genotype and an interaction (product) term between them. Four of the five SNPs previously reported by others were statistically significantly associated with increased risk of glioma in our study (rs2736100, rs4295627, rs4977756, and rs6010620); rs498872 was not associated with glioma in our study. Reporting any allergies or AIC was associated with reduced risks of glioma (allergy: adjusted OR = 0.71, 95 % CI 0.55–0.91; AIC: adjusted OR = 0.65, 95 % CI 0.47–0.90). We did not observe differential association between allergic or autoimmune conditions and glioma by genotype, and there were no statistically significant p interactions. Stratified analysis by glioma grade (low and high grade) did not suggest risk differences by disease grade. Our results do not provide evidence that allergies or AIC modulate the association between the four GWAS-identified SNPs examined and risk of glioma.}, number={10}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Safaeian, Mahboobeh and Rajaraman, Preetha and Hartge, Patricia and Yeager, Meredith and Linet, Martha and Butler, Mary Ann and Ruder, Avima M. and Purdue, Mark P. and Hsing, Ann and Beane-Freeman, Laura and et al.}, year={2013}, month={Aug}, pages={1885–1891} } @article{hou_andreotti_baccarelli_savage_hoppin_sandler_barker_zhu_hoxha_dioni_et al._2013, title={Lifetime Pesticide Use and Telomere Shortening among Male Pesticide Applicators in the Agricultural Health Study}, volume={121}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1206432}, DOI={10.1289/ehp.1206432}, abstractNote={Telomere length (TL) in surrogate tissues may be influenced by environmental exposures.We aimed to determine whether lifetime pesticides use is associated with buccal cell TL.We examined buccal cell TL in relation to lifetime use of 48 pesticides for 1,234 cancer-free white male pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of 57,310 licensed pesticide applicators. Participants provided detailed information on lifetime use of 50 pesticides at enrollment (1993-1997). Buccal cells were collected from 1999 to 2006. Relative telomere length (RTL) was measured using quantitative real-time polymerase chain reaction. We used linear regression modeling to evaluate the associations between specific pesticides and the logarithm of RTL, adjusting for age at buccal cell collection, state of residence, applicator license type, chewing tobacco use, and total lifetime days of all pesticide use.The mean RTL for participants decreased significantly in association with increased lifetime days of pesticide use for alachlor (p = 0.002), 2,4-dichlorophenoxyacetic acid (2,4-D; p = 0.004), metolachlor (p = 0.01), trifluralin (p = 0.05), permethrin (for animal application) (p = 0.02), and toxaphene (p = 0.04). A similar pattern of RTL shortening was observed with the metric lifetime intensity-weighted days of pesticide use. For dichlorodiphenyltrichloroethane (DDT), we observed significant RTL shortening for lifetime intensity-weighted days (p = 0.04), but not for lifetime days of DDT use (p = 0.08). No significant RTL lengthening was observed for any pesticide.Seven pesticides previously associated with cancer risk in the epidemiologic literature were inversely associated with RTL in buccal cell DNA among cancer-free pesticide applicators. Replication of these findings is needed because we cannot rule out chance or fully rule out bias.}, number={8}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hou, Lifang and Andreotti, Gabriella and Baccarelli, Andrea A. and Savage, Sharon and Hoppin, Jane A. and Sandler, Dale P. and Barker, Joseph and Zhu, Zhong-Zheng and Hoxha, Mirjam and Dioni, Laura and et al.}, year={2013}, month={Aug}, pages={919–924} } @article{karami_andreotti_koutros_barry_moore_han_hoppin_sandler_lubin_burdette_et al._2013, title={Pesticide Exposure and Inherited Variants in Vitamin D Pathway Genes in Relation to Prostate Cancer}, volume={22}, ISSN={1055-9965 1538-7755}, url={http://dx.doi.org/10.1158/1055-9965.EPI-12-1454}, DOI={10.1158/1055-9965.EPI-12-1454}, abstractNote={Vitamin D and its metabolites are believed to impede carcinogenesis by stimulating cell differentiation, inhibiting cell proliferation, and inducing apoptosis. Certain pesticides have been shown to deregulate vitamin D's anticarcinogenic properties. We hypothesize that certain pesticides may be linked to prostate cancer via an interaction with vitamin D genetic variants.}, number={9}, journal={Cancer Epidemiology Biomarkers & Prevention}, publisher={American Association for Cancer Research (AACR)}, author={Karami, S. and Andreotti, G. and Koutros, S. and Barry, K. H. and Moore, L. E. and Han, S. and Hoppin, J. A. and Sandler, D. P. and Lubin, J. H. and Burdette, L. A. and et al.}, year={2013}, month={Jul}, pages={1557–1566} } @article{beard_hoppin_richards_alavanja_blair_sandler_kamel_2013, title={Pesticide exposure and self-reported incident depression among wives in the Agricultural Health Study}, volume={126}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2013.06.001}, DOI={10.1016/j.envres.2013.06.001}, abstractNote={Depression in women is a public health problem. Studies have reported positive associations between pesticides and depression, but few studies were prospective or presented results for women separately.We evaluated associations between pesticide exposure and incident depression among farmers' wives in the Agricultural Health Study, a prospective cohort study in Iowa and North Carolina.We used data on 16,893 wives who did not report physician-diagnosed depression at enrollment (1993-1997) and who completed a follow-up telephone interview (2005-2010). Among these wives, 1054 reported physician diagnoses of depression at follow-up. We collected information on potential confounders and on ever use of any pesticide, 11 functional and chemical classes of pesticides, and 50 specific pesticides by wives and their husbands via self-administered questionnaires at enrollment. We used inverse probability weighting to adjust for potential confounders and to account for possible selection bias induced by the death or loss of 10,639 wives during follow-up. We used log-binomial regression models to estimate risk ratios and 95% confidence intervals.After weighting for age at enrollment, state of residence, education level, diabetes diagnosis, and drop out, wives' incident depression was positively associated with diagnosed pesticide poisoning, but was not associated with ever using any pesticide. Use of individual pesticides or functional or chemical classes of pesticides was generally not associated with wives' depression. Among wives who never used pesticides, husbands' ever use of individual pesticides or functional or chemical classes of pesticides was generally not associated with wives' incident depression.Our study adds further evidence that high level pesticide exposure, such as pesticide poisoning, is associated with increased risk of depression and sets a lower bound on the level of exposure related to depression, thereby providing reassurance that the moderate levels of pesticide exposure experienced by farmers' wives likely do not increase risk.}, journal={Environmental Research}, publisher={Elsevier BV}, author={Beard, John D. and Hoppin, Jane A. and Richards, Marie and Alavanja, Michael C.R. and Blair, Aaron and Sandler, Dale P. and Kamel, Freya}, year={2013}, month={Oct}, pages={31–42} } @article{hoppin_2013, title={Pesticides and respiratory health: where do we go from here?}, volume={71}, ISSN={1351-0711 1470-7926}, url={http://dx.doi.org/10.1136/oemed-2013-101876}, DOI={10.1136/oemed-2013-101876}, abstractNote={For centuries, researchers have focused on exposures to hays, grains and animals as primary contributors to poor respiratory outcomes in farmers and agricultural workers.1 ,2 However, growing evidence suggests that other agricultural exposures, namely pesticides, may also adversely impact respiratory health. Recent studies from around the world have suggested that pesticides may be associated with respiratory symptoms and disease, particularly asthma.3–6 However, these studies have been based on self-reported outcomes and there have been few studies using objective measures of pulmonary function.2 ,7 De Jong et al 8 report that occupational pesticide exposure is associated with poorer pulmonary function consistent with airway obstruction as measured by spirometry in two Dutch general population cohorts. These associations with pesticides were seen in both men and women and smokers and non-smokers; some associations were stronger in smokers, but not consistently so. …}, number={2}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Hoppin, Jane A}, year={2013}, month={Nov}, pages={80–80} } @article{hoppin_jaramillo_london_bertelsen_salo_sandler_zeldin_2013, title={Phthalate Exposure and Allergy in the U.S. Population: Results from NHANES 2005–2006}, volume={121}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1206211}, DOI={10.1289/ehp.1206211}, abstractNote={Background: Environmental exposures to phthalates, particularly high-molecular-weight (HMW) phthalates, are suspected to contribute to allergy.Objective: We assessed whether phthalate metabolites are associated with allergic symptoms and sensitization in a large nationally representative sample.Methods: We used data on urinary phthalate metabolites and allergic symptoms (hay fever, rhinitis, allergy, wheeze, asthma) and sensitization from participants ≥ 6 years of age in the National Health and Nutrition Examination Survey (NHANES) 2005–2006. Allergen sensitization was defined as a positive response to at least one of 19 specific IgE antigens (≥ 0.35 kU/L). Odds ratios (ORs) per one log10 unit change in phthalate concentration were estimated using logistic regression adjusting for age, race, body mass index, gender, creatinine, and cotinine. Separate analyses were conducted for children (6–17 years of age) and adults.Results: The HMW phthalate metabolite monobenzyl phthalate (MBzP) was the only metabolite positively associated with current allergic symptoms in adults (wheeze, asthma, hay fever, and rhinitis). Mono-(3-carboxypropyl) phthalate and the sum of diethylhexyl phthalate metabolites (both representing HMW phthalate exposures) were positively associated with allergic sensitization in adults. Conversely, in children, HMW phthalate metabolites were inversely associated with asthma and hay fever. Of the low-molecular-weight phthalate metabolites, monoethyl phthalate was inversely associated with allergic sensitization in adults (OR = 0.79; 95% CI: 0.70, 0.90).Conclusion: In this cross-sectional analysis of a nationally representative sample, HMW phthalate metabolites, particularly MBzP, were positively associated with allergic symptoms and sensitization in adults, but there was no strong evidence for associations between phthalates and allergy in children 6–17 years of age.Citation: Hoppin JA, Jaramillo R, London SJ, Bertelsen RJ, Salo PM, Sandler DP, Zeldin DC. 2013. Phthalate exposure and allergy in the U.S. population: results from NHANES 2005–2006. Environ Health Perspect 121:1129–1134; http://dx.doi.org/10.1289/ehp.1206211 [Online 25 June 2013].}, number={10}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, Jane A. and Jaramillo, Renee and London, Stephanie J. and Bertelsen, Randi J. and Salo, Päivi M. and Sandler, Dale P. and Zeldin, Darryl C.}, year={2013}, month={Oct}, pages={1129–1134} } @article{longnecker_harbak_kissling_hoppin_eggesbo_jusko_eide_koch_2013, title={The concentration of bisphenol A in urine is affected by specimen collection, a preservative, and handling}, volume={126}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2013.07.002}, DOI={10.1016/j.envres.2013.07.002}, abstractNote={In urine specimens that were collected from pregnant women in a large cohort, 24% contained more than 10 ng/ml of total bisphenol A (BPA), suggesting external contamination. Therefore, we conducted an investigation of the source(s) of extraneous BPA in the specimens. We found that under the conditions used to collect urine specimens in the epidemiologic study, contamination with BPA occurred, and by two separate mechanisms.}, journal={Environmental Research}, publisher={Elsevier BV}, author={Longnecker, M.P. and Harbak, K. and Kissling, G.E. and Hoppin, J.A. and Eggesbo, M. and Jusko, T.A. and Eide, J. and Koch, H.M.}, year={2013}, month={Oct}, pages={211–214} } @article{bertelsen_carlsen_calafat_hoppin_håland_mowinckel_carlsen_løvik_2013, title={Urinary Biomarkers for Phthalates Associated with Asthma in Norwegian Children}, volume={121}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1205256}, DOI={10.1289/ehp.1205256}, abstractNote={Background: High-molecular-weight phthalates in indoor dust have been associated with asthma in children, but few studies have evaluated phthalate biomarkers in association with respiratory outcomes.Objectives: We explored the association between urinary concentrations of phthalate metabolites and current asthma.Methods: In a cross-sectional analysis, 11 metabolites of 8 phthalates [including four metabolites of di(2-ethylhexyl) phthalate] were measured in one first morning void collected from 2001 through 2004 from 623 10-year-old Norwegian children. Logistic regression models controlling for urine specific gravity, sex, parental asthma, and income were used to estimate associations between current asthma and phthalate metabolite concentrations by quartiles or as log10-transformed variables.Results: Current asthma was associated with both mono(carboxyoctyl) phthalate (MCOP) and mono(carboxynonyl) phthalate (MCNP), although the association was limited to those in the highest quartile of these chemicals. The adjusted odds ratio (aOR) for current asthma was 1.9 (95% CI: 1.0, 3.3) for the highest MCOP quartile compared with the lowest quartile, and 1.3 (95% CI: 0.98, 1.7) for an interquartile-range increase. The aOR for current asthma was 2.2 (95% CI: 1.2, 4.0) for the highest MCNP quartile and 1.3 (95% CI: 1.0, 1.7) for an interquartile-range increase. The other phthalate metabolites were not associated with current asthma.Conclusions: Current asthma was associated with the highest quartiles of MCOP and MCNP, metabolites of two high molecular weight phthalates, diisononyl phthalate and diisodecyl phthalate, respectively. Given the short biological half-life of the phthalates and the cross-sectional design, our findings should be interpreted cautiously.}, number={2}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Bertelsen, Randi J. and Carlsen, Karin C. Lødrup and Calafat, Antonia M. and Hoppin, Jane A. and Håland, Geir and Mowinckel, Petter and Carlsen, Kai-Håkon and Løvik, Martinus}, year={2013}, month={Feb}, pages={251–256} } @article{buckley_palmieri_matuszewski_herring_baird_hartmann_hoppin_2012, title={Consumer product exposures associated with urinary phthalate levels in pregnant women}, volume={22}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2012.33}, DOI={10.1038/jes.2012.33}, abstractNote={Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18-38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Associations with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calculated in multiple linear regression models. Few measured factors were statistically significantly associated with phthalate levels. Individuals who used nail polish had higher levels of mono-butyl phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also associated with urinary phthalates. The proportion of variance in metabolite concentrations explained by questionnaire items ranged between 0.31 for mono-ethyl phthalate and 0.42 for mono-n-methyl phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items.}, number={5}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Buckley, Jessie P and Palmieri, Rachel T and Matuszewski, Jeanine M and Herring, Amy H and Baird, Donna D and Hartmann, Katherine E and Hoppin, Jane A}, year={2012}, month={Jul}, pages={468–475} } @article{cupul-uicab_skjaerven_haug_travlos_wilson_eggesbø_hoppin_whitworth_longnecker_2012, title={Exposure to Tobacco Smoke in Utero and Subsequent Plasma Lipids, ApoB, and CRP among Adult Women in the MoBa Cohort}, volume={120}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1104563}, DOI={10.1289/ehp.1104563}, abstractNote={Recent findings suggest that maternal smoking during pregnancy may play a role in the development of metabolic alterations in offspring during childhood. However, whether such exposure increases the risk of developing similar metabolic alterations during adulthood is uncertain.We evaluated the association of in utero exposure to maternal tobacco smoke with plasma lipids, apolipoprotein B (apoB), and C-reactive protein (CRP) in adulthood.The study was based on a subsample of the Norwegian Mother and Child Cohort Study (MoBa) and included 479 pregnant women with plasma lipids, apoB, and CRP measurements. Information on in utero exposure to tobacco smoke, personal smoking, and other factors were obtained from the women by a self-completed questionnaire at enrollment, at approximately 17 weeks of gestation.Women exposed to tobacco smoke in utero had higher triglycerides [10.7% higher; 95% confidence interval (CI): 3.9, 17.9] and lower high-density lipoprotein cholesterol (HDL) (-1.9 mg/dL; 95% CI: -4.3, 0.5) compared with unexposed women, after adjusting for age, physical activity, education, personal smoking, and current body mass index (BMI). Exposed women were also more likely to have triglycerides ≥ 200 mg/dL [adjusted odds ratio (aOR) = 2.5; 95% CI: 1.3, 5.1] and HDL < 50 mg/dL (aOR = 2.3; 95% CI: 1.1, 5.0). Low-density lipoprotein cholesterol, total cholesterol, and apoB were not associated with the exposure. CRP was increased among exposed women; however, after adjustment for BMI, the association was completely attenuated.In this population, in utero exposure to tobacco smoke was associated with high triglycerides and low HDL in adulthood, 18-44 years after exposure.}, number={11}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Cupul-Uicab, Lea A. and Skjaerven, Rolv and Haug, Kjell and Travlos, Gregory S. and Wilson, Ralph E. and Eggesbø, Merete and Hoppin, Jane A. and Whitworth, Kristina W. and Longnecker, Matthew P.}, year={2012}, month={Nov}, pages={1532–1537} } @article{racine_laditka_dmochowski_alavanja_lee_hoppin_2012, title={Farming activities and carrying and lifting: The agricultural health study}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-84862940731&partnerID=MN8TOARS}, number={1}, journal={Journal of Physical Activity and Health}, author={Racine, E.F. and Laditka, S.B. and Dmochowski, J. and Alavanja, M.C.R. and Lee, D.-C. and Hoppin, J.A.}, year={2012}, pages={39–47} } @article{endres_green_henneberger_germolec_bledsoe_beezhold_london_alavanja_beane freeman_hoppin_2012, title={Fungal and atopic sensitization are low among farmers in the Agricultural Health Study}, volume={130}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2012.04.018}, DOI={10.1016/j.jaci.2012.04.018}, abstractNote={Farm work may result in exposure to microbial bioaerosols. In agriculture, average airborne concentrations of fungal conidia are several orders of magnitude higher than in nonagricultural, indoor environments without water damage.1Eduard W. Fungal spores: a critical review of the toxicological and epidemiological evidence as a basis for occupational exposure limit setting.Crit Rev Toxicol. 2009; 39: 799-864Crossref PubMed Scopus (175) Google Scholar We used data from Iowa and North Carolina farmers to explore associations between farming activities and fungal sensitization. We analyzed serum samples from a neurobehavioral substudy of 677 male private pesticide applicators in the Agricultural Health Study (AHS).2Starks S.E. Gerr F. Kamel F. Lynch C.F. Jones M.P. Alavanja M.C. et al.Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study.Neurotoxicol Teratol. 2012; 34: 168-176Crossref PubMed Scopus (38) Google Scholar Blood was collected in 2006-2008 from male pesticide applicators who had completed all AHS interviews. Blood samples were not available for the whole cohort. Individuals were excluded if they had never been a farmer or had neurologic diseases; women were excluded because of their low prevalence in the cohort (<3%).2Starks S.E. Gerr F. Kamel F. Lynch C.F. Jones M.P. Alavanja M.C. et al.Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study.Neurotoxicol Teratol. 2012; 34: 168-176Crossref PubMed Scopus (38) Google Scholar Participants in the substudy were similar to the cohort as a whole with regard to farm history (Hoppin et al, 2012, unpublished data). The study was approved by institutional review boards of the University of Iowa, the National Institutes of Health, and its contractors. Serum samples were analyzed for total immunoglobulin E and screened for fungal positivity to a fungal-mix (mx2) by fluoroenzymeimmunoassay using ImmunoCAP 100 (Phadia AB, Uppsala, Sweden). Sensitization to other allergens was not measured. If sera were fungal-mix positive, they were tested for specific IgE to 10 fungal species (Aspergillus fumigatus, Penicillium chrysogenum, Alternaria alternata, Curvularia lunata, Epicoccum purpurascens, Phoma betae, Candida albicans, Botrytis cinerea, Fusarium proliferatum, and Cladosporium herbarum). Fungal sensitization was defined as specific IgE levels of 0.35 kU/L or more to at least 1 fungus; atopy was defined as total IgE level of 100 kU/L or more.3Burney P. Malmberg E. Chinn S. Jarvis D. Luczynska C. Lai E. The distribution of total and specific serum IgE in the European Community Respiratory Health Survey.J Allergy Clin Immunol. 1997; 99: 314-322Abstract Full Text Full Text PDF PubMed Scopus (275) Google Scholar Pesticide applicators completed 3 questionnaires about their agricultural and medical history: one at enrollment and two 5-year follow-up interviews. Farming practices included specific crops and animals raised, growing up on a farm, and years worked or lived on a farm. Data from all 3 questionnaires were used for the analysis. Exact logistic regression models were used to estimate associations with farming characteristics and fungal sensitization or atopy while controlling for state; other factors such as age and smoking did not confound the associations. The prevalence of fungal sensitization was 4%, and the prevalence of atopy was 21%. While the prevalence of atopy was greater for North Carolina farmers than for Iowa farmers (odds ratio [OR], 1.5; 95% CI, 1.0-2.1), fungal sensitization did not differ. Twenty-five percent of fungal-sensitized participants were not classified as atopic (n = 7; see Table E1 in this article’s Online Repository at www.jacionline.org). Fungal-sensitized farmers (n = 28) were slightly older than those who were not (63 years vs 61 years); however, there was no difference in the average age of the 2 groups (P = .27). Specific commodities were related to fungal sensitization (Table I). After adjusting for state, farmers who grew tobacco, orchard fruit, or raised animals, particularly cattle, were more likely to be fungal sensitized than farmers not performing these activities. Growing soybeans, field corn, or other grains was also positively associated with fungal sensitization but was not statistically significant. We lacked the ability to assess multiple crops in the same model because of the low prevalence of fungal sensitization and the high degree of correlation among crops. Sensitization to any specific fungal antigen was low, ∼2% for all farmers and between 4% and 8% when limited to those classified as atopic (Table II). Sensitization to specific fungi showed that 11 of the 28 individuals (39%) were monosensitized and 17 (61%) were multisensitized.Table IFarming characteristics and fungal sensitization and atopy among 677 farmers in the AHSEnrollment variablesFungal sensitizedOdds ratio∗Defined as total IgE level of 100 kU/L or more.95% CIAtopic (n = 14)∗Defined as total IgE level of 100 kU/L or more.Nonatopic (n = 536)Odds ratio†Adjusted for state.95% CIYes (n = 28)No (n = 649)nPercentnPercentnPercentnPercentGrew up on a farm No311681115115611 Yes2589575891.00.35.512689474891.10.62.2Years worked/lived on farm <3041515124241713125 ≥302385489761.90.67.711483398751.81.13.1Currently farming Yes2279519800.90.33.010676435810.80.51.3 No6211272034249919Crops grown Field corn2589504783.10.91110474425790.90.51.4 Soybeans2589490763.00.91010272413770.90.61.3 Hay and alfalfa1554314481.50.63.66848261491.30.82.0 Other grains1968336522.10.94.78258273511.41.02.1 Tobacco1139139213.61.1113827112211.20.71.9 Cotton51865102.00.65.911859110.50.31.1 Peanuts51864102.00.76.1141055100.80.41.5 Row crops51886131.40.53.8211570131.00.61.8 Orchard fruits4141526.92.123961023.41.48.7 Silage932153242.00.76.13424128241.30.82.2Animals raised Any animals2279415642.61.06.89265345641.30.82.0 Cattle (dairy and beef)1968308472.81.26.77251255481.40.92.1 Swine829216330.80.32.23827186350.80.51.3 Poultry4145581.80.65.315114481.30.72.3Orchard fruits are apples and peaches. Row crops are blueberries, cabbage, grapes, cucumbers, peppers, snap beans, strawberries, tomatoes, melons, and pumpkins.∗ Defined as total IgE level of 100 kU/L or more.† Adjusted for state. Open table in a new tab Table IIPrevalence of fungal sensitization to 10 fungal agents among 677 male AHS farmers, 2006-2008All farmers (n = 677)Atopic∗Defined as total IgE level of 100 kU/L or more. farmers (n = 141)nPercentnPercentAny fungal sensitization†Sensitized (specific IgE level of ≥0.35kU/L) to any fungi.2842115Eurotiales Aspergillus fumigatus142118 Penicillium chrysogenum142118Pleosporales Alternaria alternata14286 Curvularia lunata7175 Epicoccum purpurascens142118 Phoma betae142118Saccharomycetales Candida albicans142107Helotiales Botrytis cinerea7164Hypocreales Fusarium proliferatum7164Capnodiales Cladosporium herbarum7164∗ Defined as total IgE level of 100 kU/L or more.† Sensitized (specific IgE level of ≥0.35kU/L) to any fungi. Open table in a new tab Orchard fruits are apples and peaches. Row crops are blueberries, cabbage, grapes, cucumbers, peppers, snap beans, strawberries, tomatoes, melons, and pumpkins. Fungal sensitization was less common among these farmers than among white men 40 years and older from the National Health and Nutrition Examination Survey in 2005-2006.4National Center for Health Statistics, US Centers for Disease Control and Prevention. Department of Health and Human Services (CHHS)/National Health and Nutrition Examination Survey (NHANES), 2005-2006. 2006. Available from: http://www.cdc.gov/nchs/nhanes/nhanes2005-2006/nhanes05_06.htm. Accessed June 1, 2011.Google Scholar Among farmers, sensitization prevalence to both Alternaria and Aspergillus was 2% (95% CI, 1%-3%), which was lower than that in the National Health and Nutrition Examination Survey, with 7% for A alternata (95% CI, 5%-9%) and 6% for A fumigatus (95% CI, 4%-7%). Atopy prevalence was also lower (21%; 95% CI, 17%-25%) than that among the National Health and Nutrition Examination Survey participants (30%; 95% CI, 27%-33%). Other studies of agricultural workers suggest greater fungal sensitization among farmers.5Monso E. Magarolas R. Badorrey I. Radon K. Nowak D. Morera J. Occupational asthma in greenhouse flower and ornamental plant growers.Am J Respir Crit Care Med. 2002; 165: 954-960Crossref PubMed Scopus (55) Google Scholar, 6Rimac D. Macan J. Varnai V.M. Vucemilo M. Matkovic K. Prester L. et al.Exposure to poultry dust and health effects in poultry workers: impact of mould and mite allergens.Int Arch Occup Environ Health. 2010; 83: 9-19Crossref PubMed Scopus (67) Google Scholar, 7Terho E.O. Vohlonen I. Husman K. Rautalahti M. Tukiainen H. Viander M. Sensitization to storage mites and other work-related and common allergens among Finnish dairy farmers.Eur J Respir Dis Suppl. 1987; 152: 165-174PubMed Google Scholar, 8Zhang Y. Chen J. Chen Y. Dong J. Wei Q. Lou J. Environmental mycological study and allergic respiratory disease among tobacco processing workers.J Occup Health. 2005; 47: 181-187Crossref PubMed Scopus (15) Google Scholar While no studies appear to have focused on the fungal sensitization associated with specific field crops, 18% of greenhouse workers were sensitized to at least 1 of 4 fungal species as measured by the skin prick test, much higher than what we observed even though our panel included the same fungi in addition to 6 other species.5Monso E. Magarolas R. Badorrey I. Radon K. Nowak D. Morera J. Occupational asthma in greenhouse flower and ornamental plant growers.Am J Respir Crit Care Med. 2002; 165: 954-960Crossref PubMed Scopus (55) Google Scholar While our study is among the largest to characterize fungal sensitization among farmers, our analysis was limited because of the low prevalence of sensitization and the high prevalence of certain types of crop production and high correlation among these crops. Our panel contained 10 common fungal species; many, but not all, have been associated with commodity crops. If the panel included a greater diversity of species, the prevalence of sensitization may have been higher; however, given that most farmers were multisensitized to fungi, it is unlikely that the addition of other fungi would greatly alter our results. The participants were older farmers, and so a healthy worker effect is possible where sensitized farmers have been selected out of agriculture prior to sampling. Our population was not selected on the basis of respiratory disease history; thus, our lower estimates may reflect the fact that other studies may have been enriched for individuals with respiratory outcomes. The agricultural exposure history was well characterized by detailed questionnaires; however, no environmental exposure assessments were conducted. Because of the high degree of correlation between some crops, most notably corn and soybeans, and the high prevalence of growing these 2 crops, we lacked statistical power to fully evaluate whether one or both of these major crops contributed to fungal sensitization. In conclusion, this study represents one of the largest and most heterogeneous studies of fungal sensitization with regard to agricultural activities. Both fungal sensitization and atopy were low in this sample of US farmers compared with the US population. Individuals working with tobacco, orchard fruit, or animals had a higher prevalence of fungal sensitization; however, the sample size limited our ability to evaluate the influence of specific crops. Because fungal exposures differ around the world and rates of allergen sensitization differ on the basis of farming history, future studies will need to focus not only on commodities produced and specific fungal agents but also on population characteristics that may have an impact on sensitization. We thank Stuart Long for his assistance with data analysis. Findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Association of Schools of Public Health and/or the Centers for Disease Control and Prevention. Copies of questionnaires are available at www.aghealth.org/questionnaires.html. We used the P1REL201005, P3REL1090100, and AHSREL201004 releases of the AHS data set. Table E1Demographic, lifestyle, and medical characteristics of the 677 AHS farmers by fungal sensitization and atopic statusCharacteristicsFungal sensitizedAtopic (n = 141)∗Defined as total IgE level of 100 kU/L or more.Nonatopic (n = 536)Yes (n = 28)No (n = 649)Age (y) at blood draw, mean (SD)63 ± 1461 ± 1263 ± 1260 ± 12n%n%n%n%Atopy∗Defined as total IgE level of 100 kU/L or more.21751201814110000Body mass index (kg/m2) <2562112219261910219 25-30124332750654627451 >30103620031503616030Smoking history Ever smoked113927743614422742 Never smoked176137157805730857Alcohol consumption Ever165740663876233563 Never124324337543820138State Iowa134632951614328152 North Carolina155432049805725548Respiratory symptoms and diseases Hay fever13461191837279518 Wheeze in the past 12 mo124313120423010119∗ Defined as total IgE level of 100 kU/L or more. Open table in a new tab}, number={1}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Endres, Stacy M. and Green, Brett J. and Henneberger, Paul K. and Germolec, Dori R. and Bledsoe, Toni A. and Beezhold, Donald H. and London, Stephanie J. and Alavanja, Michael C. and Beane Freeman, Laura E. and Hoppin, Jane A.}, year={2012}, month={Jul}, pages={267–270.e1} } @article{goldman_kamel_ross_bhudhikanok_hoppin_korell_marras_meng_umbach_kasten_et al._2012, title={Genetic modification of the association of paraquat and Parkinson's disease}, volume={27}, ISSN={0885-3185}, url={http://dx.doi.org/10.1002/mds.25216}, DOI={10.1002/mds.25216}, abstractNote={Abstract Paraquat is one of the most widely used herbicides worldwide. It produces a Parkinson's disease (PD) model in rodents through redox cycling and oxidative stress (OS) and is associated with PD risk in humans. Glutathione transferases provide cellular protection against OS and could potentially modulate paraquat toxicity. We investigated PD risk associated with paraquat use in individuals with homozygous deletions of the genes encoding glutathione S ‐transferase M1 (GSTM1) or T1 (GSTT1). Eighty‐seven PD subjects and 343 matched controls were recruited from the Agricultural Health Study, a study of licensed pesticide applicators and spouses in Iowa and North Carolina. PD was confirmed by in‐person examination. Paraquat use and covariates were determined by interview. We genotyped subjects for homozygous deletions of GSTM1 ( GSTM1*0 ) and GSTT1 ( GSTT1*0 ) and tested interaction between paraquat use and genotype using logistic regression. Two hundred and twenty‐three (52%) subjects had GSTM1*0 , 95 (22%) had GSTT1*0 , and 73 (17%; all men) used paraquat. After adjustment for potential confounders, there was no interaction with GSTM1 . In contrast, GSTT1 genotype significantly modified the association between paraquat and PD. In men with functional GSTT1 , the odds ratio (OR) for association of PD with paraquat use was 1.5 (95% confidence interval [CI]: 0.6–3.6); in men with GSTT1*0 , the OR was 11.1 (95% CI: 3.0–44.6; P interaction: 0.027). Although replication is needed, our results suggest that PD risk from paraquat exposure might be particularly high in individuals lacking GSTT1. GSTT1*0 is common and could potentially identify a large subpopulation at high risk of PD from oxidative stressors such as paraquat. © 2012 Movement Disorder Society}, number={13}, journal={Movement Disorders}, publisher={Wiley}, author={Goldman, Samuel M. and Kamel, Freya and Ross, G. Webster and Bhudhikanok, Grace S. and Hoppin, Jane A. and Korell, Monica and Marras, Connie and Meng, Cheryl and Umbach, David M. and Kasten, Meike and et al.}, year={2012}, month={Oct}, pages={1652–1658} } @article{goldman_kamel_ross_jewell_bhudhikanok_umbach_marras_hauser_jankovic_factor_et al._2012, title={Head injury, alpha-synuclein Rep1, and Parkinson's disease}, volume={71}, ISSN={0364-5134}, url={http://dx.doi.org/10.1002/ana.22499}, DOI={10.1002/ana.22499}, abstractNote={Abstract Objective: To test the hypothesis that variability in SNCA Rep1, a polymorphic dinucleotide microsatellite in the promoter region of the gene encoding α‐synuclein, modifies the association between head injury and Parkinson's disease (PD) risk. Methods: Participants in the Farming and Movement Evaluation (FAME) and the Study of Environmental Association and Risk of Parkinsonism using Case‐Control Historical Interviews (SEARCH), 2 independent case‐control studies, were genotyped for Rep1 and interviewed regarding head injuries with loss of consciousness or concussion prior to Parkinson's disease (PD) diagnosis. Logistic regression modeling adjusted for potential confounding variables and tested interaction between Rep1 genotype and head injury. Results: Consistent with prior reports, relative to medium‐length Rep1, short Rep1 genotype was associated with reduced PD risk (pooled odds ratio [OR], 0.7; 95% confidence interval [CI], 0.5–0.9), and long Rep1 with increased risk (pooled OR, 1.4; 95% CI, 0.95–2.2). Overall, head injury was not significantly associated with PD (pooled OR, 1.3; 95% CI, 0.9–1.8). However, head injury was strongly associated with PD in those with long Rep1 (FAME OR, 5.4; 95% CI, 1.5–19; SEARCH OR, 2.3; 95% CI, 0.6–9.2; pooled OR, 3.5; 95% CI 1.4–9.2, p ‐interaction = 0.02). Individuals with both head injury and long Rep1 were diagnosed 4.9 years earlier than those with neither risk factor ( p = 0.03). Interpretation: While head injury alone was not associated with PD risk, our data suggest head injury may initiate and/or accelerate neurodegeneration when levels of synuclein are high, as in those with Rep1 expansion. Given the high population frequency of head injury, independent verification of these results is essential. ANN NEUROL 2012;71:40–48}, number={1}, journal={Annals of Neurology}, publisher={Wiley}, author={Goldman, Samuel M. and Kamel, Freya and Ross, G. Webster and Jewell, Sarah A. and Bhudhikanok, Grace S. and Umbach, David and Marras, Connie and Hauser, Robert A. and Jankovic, Joseph and Factor, Stewart A. and et al.}, year={2012}, month={Jan}, pages={40–48} } @article{hoppin_long_umbach_lubin_starks_gerr_thomas_hines_weichenthal_kamel_et al._2012, title={Lifetime organophosphorous insecticide use among private pesticide applicators in the Agricultural Health Study}, volume={22}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2012.79}, DOI={10.1038/jes.2012.79}, abstractNote={Organophosphorous insecticides (OPs) are the most commonly used insecticides in US agriculture, but little information is available regarding specific OP use by individual farmers. We describe OP use for licensed private pesticide applicators from Iowa and North Carolina in the Agricultural Health Study (AHS) using lifetime pesticide use data from 701 randomly selected male participants collected at three time periods. Of 27 OPs studied, 20 were used by >1%. Overall, 95% had ever applied at least one OP. The median number of different OPs used was 4 (maximum=13). Malathion was the most commonly used OP (74%) followed by chlorpyrifos (54%). OP use declined over time. At the first interview (1993–1997), 68% of participants had applied OPs in the past year; by the last interview (2005–2007), only 42% had. Similarly, median annual application days of OPs declined from 13.5 to 6 days. Although OP use was common, the specific OPs used varied by state, time period, and individual. Much of the variability in OP use was associated with the choice of OP, rather than the frequency or duration of application. Information on farmers’ OP use enhances our ability to characterize and understand the potential health effects of multiple OP exposures.}, number={6}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Hoppin, Jane A and Long, Stuart and Umbach, David M and Lubin, Jay H and Starks, Sarah E and Gerr, Fred and Thomas, Kent and Hines, Cynthia J and Weichenthal, Scott and Kamel, Freya and et al.}, year={2012}, month={Aug}, pages={584–592} } @article{barry_koutros_lubin_coble_barone-adesi_beane freeman_sandler_hoppin_ma_zheng_et al._2012, title={Methyl bromide exposure and cancer risk in the Agricultural Health Study}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-012-9949-2}, DOI={10.1007/s10552-012-9949-2}, abstractNote={Methyl bromide is a genotoxic soil fumigant with high acute toxicity, but unknown human carcinogenicity. Although many countries have reduced methyl bromide use because of its ozone depleting properties, some uses remain in the United States and other countries, warranting further investigation of human health effects.We used Poisson regression to calculate rate ratios (RR) and 95 % confidence intervals (CI) for associations between methyl bromide use and all cancers combined, as well as 12 specific sites, among 53,588 Agricultural Health Study pesticide applicators with follow-up from 1993 to 2007. We also evaluated interactions with a family history for four common cancers (prostate, lung, colon, and lymphohematopoietic). We categorized methyl bromide exposure based on lifetime days applied weighted by an intensity score.A total of 7,814 applicators (14.6 %) used methyl bromide, predominantly before enrollment. Based on 15 exposed cases, stomach cancer risk increased monotonically with increasing methyl bromide use (RR = 1.42; 95 % CI, 0.51-3.95 and RR = 3.13; 95 % CI, 1.25-7.80 for low and high use compared with no use; p (trend) = 0.02). No other sites displayed a significant monotonic pattern. Although we previously observed an association with prostate cancer (follow-up through 1999), the association did not persist with longer follow-up. We observed a nonsignificant elevated risk of prostate cancer with methyl bromide use among those with a family history of prostate cancer, but the interaction with a family history did not achieve statistical significance.Our results provide little evidence of methyl bromide associations with cancer risk for most sites examined; however, we observed a significant exposure-dependent increase in stomach cancer risk. Small numbers of exposed cases and declining methyl bromide use might have influenced our findings. Further study is needed in more recently exposed populations to expand on these results.}, number={6}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Barry, Kathryn Hughes and Koutros, Stella and Lubin, Jay H. and Coble, Joseph B. and Barone-Adesi, Francesco and Beane Freeman, Laura E. and Sandler, Dale P. and Hoppin, Jane A. and Ma, Xiaomei and Zheng, Tongzhang and et al.}, year={2012}, month={Apr}, pages={807–818} } @article{starks_gerr_kamel_lynch_jones_alavanja_sandler_hoppin_2012, title={Neurobehavioral function and organophosphate insecticide use among pesticide applicators in the Agricultural Health Study}, volume={34}, ISSN={0892-0362}, url={http://dx.doi.org/10.1016/j.ntt.2011.08.014}, DOI={10.1016/j.ntt.2011.08.014}, abstractNote={Although persistent decrements in cognitive function have been observed among persons who have recovered from clinically overt organophosphate (OP) pesticide poisoning, little is known about the cognitive effects of chronic OP exposures that do not result in acute poisoning. To examine associations between long-term pesticide use and neurobehavioral (NB) function, NB tests were administered to licensed pesticide applicators enrolled in the Agricultural Health Study (AHS) in Iowa and North Carolina. Between 2006 and 2008, 701 male participants completed nine NB tests to assess memory, motor speed and coordination, sustained attention, verbal learning and visual scanning and processing. Data on ever-use and lifetime days of use of 16 OP pesticides were obtained from AHS interviews conducted before testing between 1993 and 2007 and during the NB visit. The mean age of participants was 61 years (SD = 12). Associations between pesticide use and NB test performance were estimated with linear regression controlling for age and outcome-specific covariates. NB test performance was associated with lifetime days of use of some pesticides. Ethoprop was significantly associated with reduced performance on a test of motor speed and visual scanning. Malathion was significantly associated with poor performance on a test of visual scanning and processing. Conversely, we observed significantly better test performance for five OP pesticides. Specifically, chlorpyrifos, coumaphos, parathion, phorate, and tetrachlorvinphos were associated with better verbal learning and memory; coumaphos was associated with better performance on a test of motor speed and visual scanning; and parathion was associated with better performance on a test of sustained attention. Several associations varied by state. Overall, we found no consistent evidence of an association between OP pesticide use and adverse NB test performance among this older sample of pesticide applicators. Potential reasons for these mostly null results include a true absence of effect as well as possible selective participation by healthier applicators.}, number={1}, journal={Neurotoxicology and Teratology}, publisher={Elsevier BV}, author={Starks, Sarah E. and Gerr, Fred and Kamel, Freya and Lynch, Charles F. and Jones, Michael P. and Alavanja, Michael C. and Sandler, Dale P. and Hoppin, Jane A.}, year={2012}, month={Jan}, pages={168–176} } @article{whitworth_haug_baird_becher_hoppin_eggesbo_skjaerven_thomsen_longnecker_2012, title={P60—Preliminary results on subfecundity and plasma concentrations of perfluorinated compounds during pregnancy in the Norwegian Mother and Child Cohort Study, 2002–2004}, volume={33}, ISSN={0890-6238}, url={http://dx.doi.org/10.1016/j.reprotox.2011.11.094}, DOI={10.1016/j.reprotox.2011.11.094}, abstractNote={To examine associations between environmental exposure to perfluoroalkyl substances (PFASs) and ovarian hormone concentrations in naturally cycling women.E2 and P were measured in saliva samples collected daily for a single menstrual cycle and concentrations of PFASs (including perfluoroctane sulfonate [PFOS] and perfluoroctanoic acid) were measured in serum samples collected during the same cycle.Not applicable.A total of 178 healthy, naturally cycling women, aged 25–35 years.None.Mean follicular E2 (cycle days −7 to −1, where 0 is the day of ovulation); mean luteal P (cycle days +2 to 10).Among nulliparous, but not parous women, PFOS concentrations were inversely associated with E2 (β = −0.025, 95% CI −0.043, −0.007) and P (β = −0.027, 95% CI −0.048, −0.007). Similar, but weaker results were observed for perfluorooctanesulfonic acid. No associations were observed between other PFASs (including perfluoroctanoic acid) and ovarian steroid concentrations, nor were any associations noted in parous women.Our results demonstrate that PFOS and perfluorooctanesulfonic acid may be associated with decreased production of E2 and P in reproductive age women. These results suggest a possible mechanism by which PFASs affect women's health, and underscore the importance of parity in research on PFASs and women's reproductive health.}, number={4}, journal={Reproductive Toxicology}, publisher={Elsevier BV}, author={Whitworth, K.W. and Haug, L.S. and Baird, D.D. and Becher, G. and Hoppin, J.A. and Eggesbo, M. and Skjaerven, R. and Thomsen, C. and Longnecker, M.P.}, year={2012}, month={Jul}, pages={620–621} } @article{whitworth_haug_baird_becher_hoppin_skjaerven_thomsen_eggesbo_travlos_wilson_et al._2012, title={Perfluorinated Compounds and Subfecundity in Pregnant Women}, volume={23}, ISSN={1044-3983}, url={http://dx.doi.org/10.1097/EDE.0b013e31823b5031}, DOI={10.1097/EDE.0b013e31823b5031}, abstractNote={Perfluorinated compounds are ubiquitous pollutants; epidemiologic data suggest they may be associated with adverse health outcomes, including subfecundity. We examined subfecundity in relation to 2 perfluorinated compounds-perfluorooctane sulfonate (PFOS) and perfluorooctanoic acid (PFOA).}, number={2}, journal={Epidemiology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Whitworth, Kristina W. and Haug, Line S. and Baird, Donna D. and Becher, Georg and Hoppin, Jane A. and Skjaerven, Rolv and Thomsen, Cathrine and Eggesbo, Merete and Travlos, Gregory and Wilson, Ralph and et al.}, year={2012}, month={Mar}, pages={257–263} } @article{whitworth_haug_baird_becher_hoppin_skjaerven_thomsen_eggesbo_travlos_wilson_et al._2012, title={Perfluorinated Compounds in Relation to Birth Weight in the Norwegian Mother and Child Cohort Study}, volume={175}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwr459}, DOI={10.1093/aje/kwr459}, abstractNote={Perfluorooctane sulfonate and perfluorooctanoic acid are perfluorinated compounds (PFCs) widely distributed in the environment. Previous studies of PFCs and birth weight are equivocal. The authors examined this association in the Norwegian Mother and Child Cohort Study (MoBa), using data from 901 women enrolled from 2003 to 2004 and selected for a prior case-based study of PFCs and subfecundity. Maternal plasma samples were obtained around 17 weeks of gestation. Outcomes included birth weight z scores, preterm birth, small for gestational age, and large for gestational age. The adjusted birth weight z scores were slightly lower among infants born to mothers in the highest quartiles of PFCs compared with infants born to mothers in the lowest quartiles: for perfluorooctane sulfonate, β = −0.18 (95% confidence interval: −0.41, 0.05) and, for perfluorooctanoic acid, β = −0.21 (95% confidence interval: −0.45, 0.04). No clear evidence of an association with small for gestational age or large for gestational age was observed. Perfluorooctane sulfonate and perfluorooctanoic acid were each associated with decreased adjusted odds of preterm birth, although the cell counts were small. Whether some of the associations suggested by these findings may be due to a noncausal pharmacokinetic mechanism remains unclear.}, number={12}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Whitworth, Kristina W. and Haug, Line S. and Baird, Donna D. and Becher, Georg and Hoppin, Jane A. and Skjaerven, Rolv and Thomsen, Cathrine and Eggesbo, Merete and Travlos, Gregory and Wilson, Ralph and et al.}, year={2012}, month={Apr}, pages={1209–1216} } @article{starks_hoppin_kamel_lynch_jones_alavanja_sandler_gerr_2012, title={Peripheral Nervous System Function and Organophosphate Pesticide Use among Licensed Pesticide Applicators in the Agricultural Health Study}, volume={120}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1103944}, DOI={10.1289/ehp.1103944}, abstractNote={Background: Evidence is limited that long-term human exposure to organophosphate (OP) pesticides, without poisoning, is associated with adverse peripheral nervous system (PNS) function.Objective: We investigated associations between OP pesticide use and PNS function by administering PNS tests to 701 male pesticide applicators in the Agricultural Health Study (AHS).Methods: Participants completed a neurological physical examination (NPx) and electrophysiological tests as well as tests of hand strength, sway speed, and vibrotactile threshold. Self-reported information on lifetime use of 16 OP pesticides was obtained from AHS interviews and a study questionnaire. Associations between pesticide use and measures of PNS function were estimated with linear and logistic regression controlling for age and outcome-specific covariates.Results: Significantly increased odds ratios (ORs) were observed for associations between ever use of 10 of the 16 OP pesticides and one or more of six NPx outcomes. Most notably, abnormal toe proprioception was significantly associated with ever use of 6 OP pesticides, with ORs ranging from 2.03 to 3.06; monotonic increases in strength of association with increasing use was observed for 3 of the 6 pesticides. Mostly null associations were observed between OP pesticide use and electrophysiological tests, hand strength, sway speed, and vibrotactile threshold.Conclusions: This study provides some evidence that long-term exposure to OP pesticides is associated with signs of impaired PNS function among pesticide applicators.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Starks, Sarah E. and Hoppin, Jane A. and Kamel, Freya and Lynch, Charles F. and Jones, Michael P. and Alavanja, Michael C. and Sandler, Dale P. and Gerr, Fred}, year={2012}, month={Apr}, pages={515–520} } @article{kamel_umbach_bedlack_richards_watson_alavanja_blair_hoppin_schmidt_sandler_2012, title={Pesticide exposure and amyotrophic lateral sclerosis}, volume={33}, ISSN={0161-813X}, url={http://dx.doi.org/10.1016/j.neuro.2012.04.001}, DOI={10.1016/j.neuro.2012.04.001}, abstractNote={Our objectives were to summarize literature on the association of amyotrophic lateral sclerosis (ALS) with pesticides as a group and to evaluate associations of ALS with specific pesticides. We conducted a meta-analysis of published studies of ALS and pesticides as a group and investigated the association of ALS with specific pesticides, using data from the Agricultural Health Study (AHS), a cohort including 84,739 private pesticide applicators and spouses. AHS participants provided information on pesticide use at enrollment in 1993-1997. In mortality data collected through February 2010, ALS was recorded on death certificates of 41 individuals whom we compared to the remaining cohort (controls), using unconditional logistic regression adjusted for age and gender to calculate odds ratios (ORs) and 95% confidence intervals. In the meta-analysis, ALS was associated with use of pesticides as a group (1.9, 1.1-3.1). In the AHS, ALS was not associated with pesticides as a group, but was associated with use of organochlorine insecticides (OCs) (1.6, 0.8-3.5), pyrethroids (1.4, 0.6-3.4), herbicides (1.6, 0.7-3.7), and fumigants (1.8, 0.8-3.9). ORs were elevated forever use of the specific OCs aldrin (2.1, 0.8-5.1), dieldrin (2.6, 0.9-7.3), DDT (2.1, 0.9-5.0), and toxaphene (2.0, 0.8-4.9). None of these associations was statistically significant. Similar results were observed in an analysis restricted to men. In conclusion, the meta-analysis suggests that ALS risk is associated with use of pesticides as a group, and our analysis of AHS data points to OC use in particular. The latter results are novel but based on a small number of cases and require replication in other populations.}, number={3}, journal={NeuroToxicology}, publisher={Elsevier BV}, author={Kamel, Freya and Umbach, David M. and Bedlack, Richard S. and Richards, Marie and Watson, Mary and Alavanja, Michael C.R. and Blair, Aaron and Hoppin, Jane A. and Schmidt, Silke and Sandler, Dale P.}, year={2012}, month={Jun}, pages={457–462} } @article{waggoner_henneberger_kullman_umbach_kamel_beane freeman_alavanja_sandler_hoppin_2012, title={Pesticide use and fatal injury among farmers in the Agricultural Health Study}, volume={86}, ISSN={0340-0131 1432-1246}, url={http://dx.doi.org/10.1007/s00420-012-0752-x}, DOI={10.1007/s00420-012-0752-x}, abstractNote={To assess whether pesticide use practices were associated with injury mortality among 51,035 male farmers from NC and IA enrolled in the Agricultural Health Study.We used Cox proportional hazards models adjusted for age and state to estimate fatal injury risk associated with self-reported use of 49 specific pesticides, personal protective equipment, specific types of farm machinery, and other farm factors collected 1-15 years preceding death. Cause-specific mortality was obtained through linkage to mortality registries.We observed 338 injury fatalities over 727,543 person-years of follow-up (1993-2008). Fatal injuries increased with days/year of pesticide application, with the highest risk among those with 60+ days of pesticide application annually [hazard ratio (HR) = 1.87; 95% confidence interval (CI) = 1.10, 3.18]. Chemical-resistant glove use was associated with decreased risk (HR = 0.73; 95% CI = 0.58, 0.93), but adjusting for glove use did not substantially change estimates for individual pesticides or pesticide use overall. Herbicides were associated with fatal injury, even after adjusting for operating farm equipment, which was independently associated with fatal injury. Ever use of five of 18 herbicides (2,4,5-T, paraquat, alachlor, metribuzin, and butylate) were associated with elevated risk. In addition, 2,4-D and cyanazine were associated with fatal injury in exposure-response analyses. There was no evidence of confounding of these results by other herbicides.The association between application of pesticides, particularly certain herbicides, and fatal injuries among farmers should be interpreted cautiously but deserves further evaluation, with particular focus on understanding timing of pesticide use and fatal injury.}, number={2}, journal={International Archives of Occupational and Environmental Health}, publisher={Springer Science and Business Media LLC}, author={Waggoner, Jenna K. and Henneberger, Paul K. and Kullman, Greg J. and Umbach, David M. and Kamel, Freya and Beane Freeman, Laura E. and Alavanja, Michael C. R. and Sandler, Dale P. and Hoppin, Jane A.}, year={2012}, month={Mar}, pages={177–187} } @article{beane freeman_deroos_koutros_blair_ward_alavanja_hoppin_2012, title={Poultry and livestock exposure and cancer risk among farmers in the agricultural health study}, volume={23}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-012-9921-1}, DOI={10.1007/s10552-012-9921-1}, abstractNote={The purpose of this study is to evaluate cancer risk associated with raising animals as commodities, which is associated with a variety of exposures, such as infectious agents and endotoxins.Information was available for 49,884 male farmers in the Agricultural Health Study, who reported livestock and poultry production at enrollment (1993-1997). Cancer incidence data were obtained through annual linkage to state registries. Using Poisson regression analyses, we evaluated whether the number and type of animals raised on the farm impacted cancer risk.Overall, 31,848 (63.8%) male farmers reported raising any animals. Lung cancer risk decreased with increasing number of livestock on the farm (p trend = 0.04) and with raising poultry (Relative Risk (RR) = 0.6; 95% confidence interval (CI): 0.4-0.97). Raising poultry was associated with an increased risk of colon cancer (RR = 1.4; 95% CI: 0.99-2.0) with further increased with larger flocks (p trend = 0.02). Risk of non-Hodgkin lymphoma was also elevated in those who raised poultry (RR = 1.6; 95% CI: 1.0-2.4), but there was no evidence of increased risk with larger flocks (p trend = 0.5). Raising sheep was associated with a significantly increased risk of multiple myeloma (RR = 4.9; 95% CI: 2.4-12.0). Performing veterinary services increased the risk of Hodgkin lymphoma (RR = 12.2; 95% CI: 1.6-96.3).We observed an inverse association between raising poultry and livestock and lung cancer risk and some evidence of increased risk of specific lymphohematopoietic malignancies with specific types of animals and performing veterinary services. Further research into associations between raising animals and cancer risk should focus on identification of etiologic agents.}, number={5}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Beane Freeman, Laura E. and DeRoos, Anneclaire J. and Koutros, Stella and Blair, Aaron and Ward, Mary H. and Alavanja, Michael and Hoppin, Jane A.}, year={2012}, month={Mar}, pages={663–670} } @article{koutros_beane freeman_lubin_heltshe_andreotti_barry_dellavalle_hoppin_sandler_lynch_et al._2012, title={Risk of Total and Aggressive Prostate Cancer and Pesticide Use in the Agricultural Health Study}, volume={177}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kws225}, DOI={10.1093/aje/kws225}, abstractNote={Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993–2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; Ptrend < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; Ptrend = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; Ptrend = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; Ptrend = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer.}, number={1}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Koutros, Stella and Beane Freeman, Laura E. and Lubin, Jay H. and Heltshe, Sonya L. and Andreotti, Gabriella and Barry, Kathryn Hughes and DellaValle, Curt T. and Hoppin, Jane A. and Sandler, Dale P. and Lynch, Charles F. and et al.}, year={2012}, month={Nov}, pages={59–74} } @article{dellavalle_hoppin_hines_andreotti_alavanja_2012, title={Risk-Accepting Personality and Personal Protective Equipment Use Within the Agricultural Health Study}, volume={17}, ISSN={1059-924X 1545-0813}, url={http://dx.doi.org/10.1080/1059924X.2012.686390}, DOI={10.1080/1059924X.2012.686390}, abstractNote={ABSTRACT Pesticide exposures can be reduced by use of personal protective equipment as well as proper mixing and application practices. The authors examined the effects of risk-accepting personality on personal protective equipment (PPE) use and mixing and application practices among private pesticide applicators and their spouses within the Agricultural Health Study (AHS) in Iowa and North Carolina and commercial applicators in Iowa. The AHS follow-up questionnaire included four questions designed to assess attitudes toward risk. Analysis was limited to those who were currently working on a farm or registered as a commercial applicator and indicated current pesticide use (n = 25,166). Respondents who answered three or more questions in the affirmative (private applicators: n = 4160 [21%]; commercial applicators: n = 199 [14%]; spouses: n = 829 [23%]) were classified as having a risk-accepting personality. Logistic regression was used to evaluate specific work practices associated with risk-accepting attitudes. Among private applicators, the likelihood of using any PPE when mixing or loading pesticides was lower among risk-acceptors compared to risk-averse individuals (odds ratio [OR] = 0.72, 95% confidence interval [CI]: 0.65–0.79). A similar relationship was observed among commercial applicators (OR = 0.77, 95% CI: 0.34–1.77) but not among spouses (OR = 1.09, 95% CI: 0.90–1.33). Among private applicators, risk-acceptors were more likely than the risk-averse to apply pesticides within 50 feet of the home (OR = 1.21, 95% CI: 1.01–1.44), compared to further than ¼ mile. These findings suggest that the decisions to use personal protective equipment and properly handle/apply pesticides may be driven by risk-accepting personality traits. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of Agromedicine for the following free supplemental resource: Adjusted odds ratios of PPE use and risk accepting personality traits among participants currently applying pesticides in the Agricultural Health Study (1999–2005)]}, number={3}, journal={Journal of Agromedicine}, publisher={Informa UK Limited}, author={DellaValle, Curt T. and Hoppin, Jane A. and Hines, Cynthia J. and Andreotti, Gabriella and Alavanja, Michael C. R.}, year={2012}, month={Jul}, pages={264–276} } @article{andreotti_koutros_berndt_hughes barry_hou_hoppin_sandler_lubin_burdette_yuenger_et al._2012, title={The Interaction between Pesticide Use and Genetic Variants Involved in Lipid Metabolism on Prostate Cancer Risk}, volume={2012}, ISSN={1687-8558 1687-8566}, url={http://dx.doi.org/10.1155/2012/358076}, DOI={10.1155/2012/358076}, abstractNote={Background . Lipid metabolism processes have been implicated in prostate carcinogenesis. Since several pesticides are lipophilic or are metabolized via lipid-related mechanisms, they may interact with variants of genes in the lipid metabolism pathway. Methods . In a nested case-control study of 776 cases and 1444 controls from the Agricultural Health Study (AHS), a prospective cohort study of pesticide applicators, we examined the interactions between 39 pesticides (none, low, and high exposure) and 220 single nucleotide polymorphisms (SNPs) in 59 genes. The false discovery rate (FDR) was used to account for multiple comparisons. Results . We found 17 interactions that displayed a significant monotonic increase in prostate cancer risk with pesticide exposure in one genotype and no significant association in the other genotype. The most noteworthy association was for ALOXE3 rs3027208 and terbufos, such that men carrying the T allele who were low users had an OR of 1.86 (95% CI = 1.16–2.99) and high users an OR of 2.00 (95% CI = 1.28–3.15) compared to those with no use of terbufos, while men carrying the CC genotype did not exhibit a significant association. Conclusion . Genetic variation in lipid metabolism genes may modify pesticide associations with prostate cancer; however our results require replication.}, journal={Journal of Cancer Epidemiology}, publisher={Hindawi Limited}, author={Andreotti, Gabriella and Koutros, Stella and Berndt, Sonja I. and Hughes Barry, Kathryn and Hou, Lifang and Hoppin, Jane A. and Sandler, Dale P. and Lubin, Jay H. and Burdette, Laurie A. and Yuenger, Jeffrey and et al.}, year={2012}, pages={1–11} } @article{heltshe_lubin_koutros_coble_ji_alavanja_blair_sandler_hines_thomas_et al._2012, title={Using multiple imputation to assign pesticide use for non-responders in the follow-up questionnaire in the Agricultural Health Study}, volume={22}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2012.31}, DOI={10.1038/jes.2012.31}, abstractNote={The Agricultural Health Study (AHS), a large prospective cohort, was designed to elucidate associations between pesticide use and other agricultural exposures and health outcomes. The cohort includes 57,310 pesticide applicators who were enrolled between 1993 and 1997 in Iowa and North Carolina. A follow-up questionnaire administered 5 years later was completed by 36,342 (63%) of the original participants. Missing pesticide use information from participants who did not complete the second questionnaire impedes both long-term pesticide exposure estimation and statistical inference of risk for health outcomes. Logistic regression and stratified sampling were used to impute key variables related to the use of specific pesticides for 20,968 applicators who did not complete the second questionnaire. To assess the imputation procedure, a 20% random sample of participants was withheld for comparison. The observed and imputed prevalence of any pesticide use in the holdout dataset were 85.7% and 85.3%, respectively. The distribution of prevalence and days/year of use for specific pesticides were similar across observed and imputed in the holdout sample. When appropriately implemented, multiple imputation can reduce bias and increase precision and can be more valid than other missing data approaches.}, number={4}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Heltshe, Sonya L and Lubin, Jay H and Koutros, Stella and Coble, Joseph B and Ji, Bu-Tian and Alavanja, Michael C R and Blair, Aaron and Sandler, Dale P and Hines, Cynthia J and Thomas, Kent W and et al.}, year={2012}, month={May}, pages={409–416} } @article{leon_freeman_douwes_hoppin_kromhout_lebailly_nordby_schenker_schüz_waring_et al._2011, title={AGRICOH: A Consortium of Agricultural Cohorts}, volume={8}, ISSN={1660-4601}, url={http://dx.doi.org/10.3390/ijerph8051341}, DOI={10.3390/ijerph8051341}, abstractNote={AGRICOH is a recently formed consortium of agricultural cohort studies involving 22 cohorts from nine countries in five continents: South Africa (1), Canada (3), Costa Rica (2), USA (6), Republic of Korea (1), New Zealand (2), Denmark (1), France (3) and Norway (3). The aim of AGRICOH, initiated by the US National Cancer Institute (NCI) and coordinated by the International Agency for Research on Cancer (IARC), is to promote and sustain collaboration and pooling of data to investigate the association between a wide range of agricultural exposures and a wide range of health outcomes, with a particular focus on associations that cannot easily be addressed in individual studies because of rare exposures (e.g., use of infrequently applied chemicals) or relatively rare outcomes (e.g., certain types of cancer, neurologic and auto-immune diseases). To facilitate future projects the need for data harmonization of selected variables is required and is underway. Altogether, AGRICOH provides excellent opportunities for studying cancer, respiratory, neurologic, and auto-immune diseases as well as reproductive and allergic disorders, injuries and overall mortality in association with a wide array of exposures, prominent among these the application of pesticides.}, number={5}, journal={International Journal of Environmental Research and Public Health}, publisher={MDPI AG}, author={Leon, Maria E. and Freeman, Laura E. Beane and Douwes, Jeroen and Hoppin, Jane A. and Kromhout, Hans and Lebailly, Pierre and Nordby, Karl-Christian and Schenker, Marc and Schüz, Joachim and Waring, Stephen C. and et al.}, year={2011}, month={Apr}, pages={1341–1357} } @article{salo_calatroni_gergen_hoppin_sever_jaramillo_arbes_zeldin_2011, title={Allergy-related outcomes in relation to serum IgE: Results from the National Health and Nutrition Examination Survey 2005-2006}, volume={127}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2010.12.1106}, DOI={10.1016/j.jaci.2010.12.1106}, abstractNote={The National Health and Nutrition Examination Survey (NHANES) 2005-2006 was the first population-based study to investigate levels of serum total and allergen-specific IgE in the general US population.We estimated the prevalence of allergy-related outcomes and examined relationships between serum IgE levels and these outcomes in a representative sample of the US population.Data for this cross-sectional analysis were obtained from NHANES 2005-2006. Study subjects aged 6 years and older (n = 8086) had blood taken for measurement of total IgE and 19 specific IgE levels against common aeroallergens, including Alternaria alternata, Aspergillus fumigatus, Bermuda grass, birch, oak, ragweed, Russian thistle, rye grass, cat dander, cockroach, dog dander, dust mite (Dermatophagoides farinae and Dermatophagoides pteronyssinus), mouse and rat urine proteins, and selected foods (egg white, cow's milk, peanut, and shrimp). Serum samples were analyzed for total and allergen-specific IgE by using the Pharmacia CAP System. Information on allergy-related outcomes and demographics was collected by questionnaire.In NHANES 2005-2006, 6.6% reported current hay fever, and 23.5% had current allergies. Allergy-related outcomes increased with increasing total IgE levels (adjusted odds ratios for a 10-fold increase in total IgE level of 1.86 [95% CI, 1.44-2.41] for hay fever and 1.64 [95% CI, 1.41-1.91] for allergies). Increased levels of plant-, pet-, and mold-specific IgE contributed independently to allergy-related symptoms. The greatest increase in odds was observed for hay fever and plant-specific IgE (adjusted odds ratio, 4.75; 95% CI, 3.83-5.88).In the US population self-reported allergy symptoms are most consistently associated with increased levels of plant-, pet-, and mold-specific IgE.}, number={5}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Salo, Päivi M. and Calatroni, Agustin and Gergen, Peter J. and Hoppin, Jane A. and Sever, Michelle L. and Jaramillo, Renee and Arbes, Samuel J., Jr. and Zeldin, Darryl C.}, year={2011}, month={May}, pages={1226–1235.e7} } @article{coble_thomas_hines_hoppin_dosemeci_curwin_lubin_freeman_blair_sandler_et al._2011, title={An Updated Algorithm for Estimation of Pesticide Exposure Intensity in the Agricultural Health Study}, volume={8}, ISSN={1660-4601}, url={http://dx.doi.org/10.3390/ijerph8124608}, DOI={10.3390/ijerph8124608}, abstractNote={An algorithm developed to estimate pesticide exposure intensity for use in epidemiologic analyses was revised based on data from two exposure monitoring studies. In the first study, we estimated relative exposure intensity based on the results of measurements taken during the application of the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) (n = 88) and the insecticide chlorpyrifos (n = 17). Modifications to the algorithm weighting factors were based on geometric means (GM) of post-application urine concentrations for applicators grouped by application method and use of chemically-resistant (CR) gloves. Measurement data from a second study were also used to evaluate relative exposure levels associated with airblast as compared to hand spray application methods. Algorithm modifications included an increase in the exposure reduction factor for use of CR gloves from 40% to 60%, an increase in the application method weight for boom spray relative to in-furrow and for air blast relative to hand spray, and a decrease in the weight for mixing relative to the new weights assigned for application methods. The weighting factors for the revised algorithm now incorporate exposure measurements taken on Agricultural Health Study (AHS) participants for the application methods and personal protective equipment (PPE) commonly reported by study participants.}, number={12}, journal={International Journal of Environmental Research and Public Health}, publisher={MDPI AG}, author={Coble, Joseph and Thomas, Kent W. and Hines, Cynthia J. and Hoppin, Jane A. and Dosemeci, Mustafa and Curwin, Brian and Lubin, Jay H. and Freeman, Laura E. Beane and Blair, Aaron and Sandler, Dale P. and et al.}, year={2011}, month={Dec}, pages={4608–4622} } @article{freeman_rusiecki_hoppin_lubin_koutros_andreotti_zahm_hines_coble_barone-adesi_et al._2011, title={Atrazine and Cancer Incidence Among Pesticide Applicators in the Agricultural Health Study (1994–2007)}, volume={119}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1103561}, DOI={10.1289/ehp.1103561}, abstractNote={Background: Atrazine is a triazine herbicide used widely in the United States. Although it is an animal carcinogen, the mechanism in rodents does not appear to operate in humans. Few epidemiologic studies have provided evidence for an association.Methods: The Agricultural Health Study (AHS) is a prospective cohort that includes 57,310 licensed pesticide applicators. In this report, we extend a previous AHS analysis of cancer risk associated with self-reported atrazine use with six additional years of follow-up and more than twice as many cancer cases. Using Poisson regression, we calculated relative risk estimates and 95% confidence intervals for lifetime use of atrazine and intensity-weighted lifetime days, which accounts for factors that impact exposure.Results: Overall, 36,357 (68%) of applicators reported using atrazine, among whom there were 3,146 cancer cases. There was no increase among atrazine users in overall cancer risk or at most cancer sites in the higher exposure categories compared with the lowest. Based on 29 exposed cases of thyroid cancer, there was a statistically significant risk in the second and fourth quartiles of intensity-weighted lifetime days. There was a similar pattern for lifetime days, but neither the risk estimates nor the trend were statistically significant and for neither metric was the trend monotonic.Conclusions: Overall, there was no consistent evidence of an association between atrazine use and any cancer site. There was a suggestion of increased risk of thyroid cancer, but these results are based on relatively small numbers and minimal supporting evidence.}, number={9}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Freeman, Laura E. Beane and Rusiecki, Jennifer A. and Hoppin, Jane A. and Lubin, Jay H. and Koutros, Stella and Andreotti, Gabriella and Zahm, Shelia Hoar and Hines, Cynthia J. and Coble, Joseph B. and Barone-Adesi, Francesco and et al.}, year={2011}, month={Sep}, pages={1253–1259} } @article{barry_koutros_berndt_andreotti_hoppin_sandler_burdette_yeager_freeman_lubin_et al._2011, title={Genetic Variation in Base Excision Repair Pathway Genes, Pesticide Exposure, and Prostate Cancer Risk}, volume={119}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1103454}, DOI={10.1289/ehp.1103454}, abstractNote={Previous research indicates increased prostate cancer risk for pesticide applicators and pesticide manufacturing workers. Although underlying mechanisms are unknown, evidence suggests a role of oxidative DNA damage.Because base excision repair (BER) is the predominant pathway involved in repairing oxidative damage, we evaluated interactions between 39 pesticides and 394 tag single-nucleotide polymorphisms (SNPs) for 31 BER genes among 776 prostate cancer cases and 1,444 male controls in a nested case-control study of white Agricultural Health Study (AHS) pesticide applicators.We used likelihood ratio tests from logistic regression models to determine p-values for interactions between three-level pesticide exposure variables (none/low/high) and SNPs (assuming a dominant model), and the false discovery rate (FDR) multiple comparison adjustment approach.The interaction between fonofos and rs1983132 in NEIL3 [nei endonuclease VIII-like 3 (Escherichia coli)], which encodes a glycosylase that can initiate BER, was the most significant overall [interaction p-value (pinteract) = 9.3 × 10-6; FDR-adjusted p-value = 0.01]. Fonofos exposure was associated with a monotonic increase in prostate cancer risk among men with CT/TT genotypes for rs1983132 [odds ratios (95% confidence intervals) for low and high use compared with no use were 1.65 (0.91, 3.01) and 3.25 (1.78, 5.92), respectively], whereas fonofos was not associated with prostate cancer risk among men with the CC genotype. Carbofuran and S-ethyl dipropylthiocarbamate (EPTC) interacted similarly with rs1983132; however, these interactions did not meet an FDR < 0.2.Our significant finding regarding fonofos is consistent with previous AHS findings of increased prostate cancer risk with fonofos exposure among those with a family history of prostate cancer. Although requiring replication, our findings suggest a role of BER genetic variation in pesticide-associated prostate cancer risk.}, number={12}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Barry, Kathryn Hughes and Koutros, Stella and Berndt, Sonja I. and Andreotti, Gabriella and Hoppin, Jane A. and Sandler, Dale P. and Burdette, Laurie A. and Yeager, Meredith and Freeman, Laura E. Beane and Lubin, Jay H. and et al.}, year={2011}, month={Dec}, pages={1726–1732} } @article{starks_gerr_kamel_lynch_alavanja_sandler_hoppin_2011, title={High pesticide exposure events and central nervous system function among pesticide applicators in the Agricultural Health Study}, volume={85}, ISSN={0340-0131 1432-1246}, url={http://dx.doi.org/10.1007/s00420-011-0694-8}, DOI={10.1007/s00420-011-0694-8}, abstractNote={While acute pesticide poisoning can be associated with persistent adverse central nervous system (CNS) effects, little is known about the effect of one or more episodic and unusually high pesticide exposure events (HPEE) that typically do not result in acute poisoning. The objective of this investigation was to examine the association between ever having an HPEE and CNS function among licensed pesticide applicators enrolled in the Agricultural Health Study (AHS).In 2006-2008, 693 male participants with no history of a physician-diagnosed pesticide poisoning completed nine neurobehavioral tests to assess memory, motor speed, sustained attention, verbal learning, and visual scanning and processing. Information on ever having an HPEE and pesticide poisonings was obtained from previous AHS interviews. Associations between ever having an HPEE and neurobehavioral outcomes were estimated with linear regression controlling for age and outcome-specific covariates.A history of ever having an HPEE was reported by 156 (23%) participants. Adverse associations were observed between ever having an HPEE and two of the nine neurobehavioral tests. On a test of visual scanning and processing (Digit-Symbol), participants who ever had an HPEE were 4.2 s slower (95% CI: -7.27, -1.11) than those without an HPEE, equivalent to the effect of 3.9 years of age in this population. On a test of visual scanning and motor speed (Sequences A), participants who ever had an HPEE were 2.5 s slower (95% CI: -4.53, -0.41) than those without an HPEE, equivalent to the effect of 3.9 years of age. No significant associations were observed between participants who ever had an HPEE and the remaining neurobehavioral tests.One or more HPEE may contribute to adverse CNS outcomes independent of diagnosed pesticide poisoning.}, number={5}, journal={International Archives of Occupational and Environmental Health}, publisher={Springer Science and Business Media LLC}, author={Starks, Sarah E. and Gerr, Fred and Kamel, Freya and Lynch, Charles F. and Alavanja, Michael C. and Sandler, Dale P. and Hoppin, Jane A.}, year={2011}, month={Sep}, pages={505–515} } @article{blair_thomas_coble_sandler_hines_lynch_knott_purdue_zahm_alavanja_et al._2011, title={Impact of pesticide exposure misclassification on estimates of relative risks in the Agricultural Health Study}, volume={68}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.2010.059469}, DOI={10.1136/oem.2010.059469}, abstractNote={Background The Agricultural Health Study (AHS) is a prospective study of licensed pesticide applicators and their spouses in Iowa and North Carolina. We evaluate the impact of occupational pesticide exposure misclassification on relative risks using data from the cohort and the AHS Pesticide Exposure Study (AHS/PES). Methods We assessed the impact of exposure misclassification on relative risks using the range of correlation coefficients observed between measured post-application urinary levels of 2,4-dichlorophenoxyacetic acid (2,4-D) and a chlorpyrifos metabolite and exposure estimates based on an algorithm from 83 AHS pesticide applications. Results Correlations between urinary levels of 2,4-D and a chlorpyrifos metabolite and algorithm estimated intensity scores were about 0.4 for 2,4-D (n=64), 0.8 for liquid chlorpyrifos (n=4) and 0.6 for granular chlorpyrifos (n=12). Correlations of urinary levels with kilograms of active ingredient used, duration of application, or number of acres treated were lower and ranged from −0.36 to 0.19. These findings indicate that a priori expert-derived algorithm scores were more closely related to measured urinary levels than individual exposure determinants evaluated here. Estimates of potential bias in relative risks based on the correlations from the AHS/PES indicate that non-differential misclassification of exposure using the algorithm would bias estimates towards the null, but less than that from individual exposure determinants. Conclusions Although correlations between algorithm scores and urinary levels were quite good (ie, correlations between 0.4 and 0.8), exposure misclassification would still bias relative risk estimates in the AHS towards the null and diminish study power.}, number={7}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Blair, A. and Thomas, K. and Coble, J. and Sandler, D. P. and Hines, C. J. and Lynch, C. F. and Knott, C. and Purdue, M. P. and Zahm, S. H. and Alavanja, M. C. R. and et al.}, year={2011}, month={Jan}, pages={537–541} } @article{fortier_doiron_little_ferretti_l’heureux_stolk_knoppers_hudson_burton_2011, title={Is rigorous retrospective harmonization possible? Application of the DataSHaPER approach across 53 large studies}, volume={40}, ISSN={1464-3685 0300-5771}, url={http://dx.doi.org/10.1093/ije/dyr106}, DOI={10.1093/ije/dyr106}, abstractNote={Proper understanding of the roles of, and interactions between genetic, lifestyle, environmental and psycho-social factors in determining the risk of development and/or progression of chronic diseases requires access to very large high-quality databases. Because of the financial, technical and time burdens related to developing and maintaining very large studies, the scientific community is increasingly synthesizing data from multiple studies to construct large databases. However, the data items collected by individual studies must be inferentially equivalent to be meaningfully synthesized. The DataSchema and Harmonization Platform for Epidemiological Research (DataSHaPER; http://www.datashaper.org) was developed to enable the rigorous assessment of the inferential equivalence, i.e. the potential for harmonization, of selected information from individual studies.This article examines the value of using the DataSHaPER for retrospective harmonization of established studies. Using the DataSHaPER approach, the potential to generate 148 harmonized variables from the questionnaires and physical measures collected in 53 large population-based studies (6.9 million participants) was assessed. Variable and study characteristics that might influence the potential for data synthesis were also explored.Out of all assessment items evaluated (148 variables for each of the 53 studies), 38% could be harmonized. Certain characteristics of variables (i.e. relative importance, individual targeted, reference period) and of studies (i.e. observational units, data collection start date and mode of questionnaire administration) were associated with the potential for harmonization. For example, for variables deemed to be essential, 62% of assessment items paired could be harmonized.The current article shows that the DataSHaPER provides an effective and flexible approach for the retrospective harmonization of information across studies. To implement data synthesis, some additional scientific, ethico-legal and technical considerations must be addressed. The success of the DataSHaPER as a harmonization approach will depend on its continuing development and on the rigour and extent of its use. The DataSHaPER has the potential to take us closer to a truly collaborative epidemiology and offers the promise of enhanced research potential generated through synthesized databases.}, number={5}, journal={International Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Fortier, Isabel and Doiron, Dany and Little, Julian and Ferretti, Vincent and L’Heureux, François and Stolk, Ronald P and Knoppers, Bartha M and Hudson, Thomas J and Burton, Paul R}, year={2011}, month={Jul}, pages={1314–1328} } @article{mirabelli_hoppin_chatterjee_isom_chen_grzywacz_howard_quandt_vallejos_arcury_2011, title={Job Activities and Respiratory Symptoms Among Farmworkers in North Carolina}, volume={66}, ISSN={1933-8244 2154-4700}, url={http://dx.doi.org/10.1080/19338244.2010.539637}, DOI={10.1080/19338244.2010.539637}, abstractNote={ABSTRACT Respiratory health is an important component of the ability to perform physically demanding work. The authors assessed respiratory symptom prevalence among Latino farmworkers engaged in crop production, and investigated work activities as risk factors for respiratory symptoms. During June to September 2008, 122 farmworkers completed up to 3 questionnaires. The authors estimated associations between work activities and wheezing symptoms using alternating logistic regression, controlling for age and smoking. At the first data collection, 29 (24%) farmworkers reported ever wheezing and 10 (8%) reported wheezing within the past month. Though not statistically significant, the odds of wheezing were elevated for individuals who reported performing tobacco-related work in the last 3 days. The odds were decreased among individuals who reported harvesting activities (odds ratio: 0.3, 95% confidence interval: 0.1, 1.0). Among Latino farmworkers, respiratory symptoms may be associated with work activities. KEYWORDS: agricultureasthmaepidemiologyoccupational lung diseaserespiratory diseases Acknowledgments This work was supported by the National Institutes of Health, National Institute of Environmental Health Sciences (grant number: R01ES008739) and the Intramural Research Program of the National Institutes of Health, National Institute of Environmental Health Sciences (grant number: Z01ES049030).}, number={3}, journal={Archives of Environmental & Occupational Health}, publisher={Informa UK Limited}, author={Mirabelli, Maria C. and Hoppin, Jane A. and Chatterjee, Arjun B. and Isom, Scott and Chen, Haiying and Grzywacz, Joseph G. and Howard, Timothy D. and Quandt, Sara A. and Vallejos, Quirina M. and Arcury, Thomas A.}, year={2011}, month={Jul}, pages={178–182} } @article{davis_kamel_hoppin_alavanja_freeman_gray_nelson_silbergeld_2011, title={Neurologic Symptoms Associated With Raising Poultry and Swine Among Participants in the Agricultural Health Study}, volume={53}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e31820805d5}, DOI={10.1097/JOM.0b013e31820805d5}, abstractNote={Objective: Guillain-Barré Syndrome (GBS) is the leading cause of acute peripheral neuropathy worldwide, often associated with recent foodborne infection with Campylobacter jejuni. In this cross-sectional analysis of data from the Agricultural Health Study, we tested whether swine and poultry exposure were associated with increased prevalence of GBS-like neurologic symptoms. Methods: Using multivariate analysis, we tested the symptoms such as numbness and weakness, relevant to inflammatory peripheral neuropathies, among farmers with self-reported occupational poultry or swine exposure compared with farmers who reported no occupational animal exposure. Results: Among swine farmers/workers, prevalence of weakness and numbness were increased (P < 0.05). Among poultry farmers/workers, prevalence of weakness and numbness were increased, but increased prevalence of weakness was not statistically significant. Conclusions: Occupational contact with live poultry or swine, potentially related to C. jejuni exposure, was associated with increased reporting of GBS-like symptoms.}, number={2}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Davis, Meghan F. and Kamel, Freya and Hoppin, Jane A. and Alavanja, Michael CR and Freeman, Laura Beane and Gray, Gregory C. and Nelson, Kenrad and Silbergeld, Ellen}, year={2011}, month={Feb}, pages={190–195} } @article{hoppin_jaramillo_salo_sandler_london_zeldin_2011, title={Questionnaire Predictors of Atopy in a US Population Sample: Findings From the National Health and Nutrition Examination Survey, 2005-2006}, volume={173}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwq392}, DOI={10.1093/aje/kwq392}, abstractNote={Allergic conditions and biochemical measures are both used to characterize atopy. To assess questionnaires' ability to predict biochemical measures of atopy, the authors used data on 5 allergic conditions (allergy, hay fever, eczema, rhinitis, and itchy rash) and serum-specific immunoglobulin E (IgE) levels from the 2005–2006 National Health and Nutrition Examination Survey. Atopy was defined as 1 or more positive specific IgEs (≥0.35 kU/L). Questionnaire responses were assessed for sensitivity, specificity, and positive and negative predictive values for atopy. In this population-based US sample, 44% of participants were specific IgE-positive and 53% reported at least 1 allergic condition. Discordance between atopy and allergic conditions was considerable; 37% of persons with atopy reported no allergic condition, and 48% of persons who reported an allergic condition were not atopic. Thus, no combination of self-reported allergic conditions achieved both high sensitivity and high specificity for IgE. The positive predictive value of reported allergic conditions for atopy ranged from 50% for eczema to 72% for hay fever, while the negative predictive value ranged from 57% for eczema to 65% for any condition. Given the high proportion of asymptomatic participants who were specific IgE-positive and persons who reported allergic conditions but were specific IgE-negative, it is unlikely that questionnaires will ever capture the same participants as those found to be atopic by biochemical measures.}, number={5}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Hoppin, J. A. and Jaramillo, R. and Salo, P. and Sandler, D. P. and London, S. J. and Zeldin, D. C.}, year={2011}, month={Jan}, pages={544–552} } @article{tanner_kamel_ross_hoppin_goldman_korell_marras_bhudhikanok_kasten_chade_et al._2011, title={Rotenone, Paraquat, and Parkinson’s Disease}, volume={119}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1002839}, DOI={10.1289/ehp.1002839}, abstractNote={BackgroundMitochondrial dysfunction and oxidative stress are pathophysiologic mechanisms implicated in experimental models and genetic forms of Parkinson's disease (PD). Certain pesticides may affect these mechanisms, but no pesticide has been definitively associated with PD in humans.ObjectivesOur goal was to determine whether pesticides that cause mitochondrial dysfunction or oxidative stress are associated with PD or clinical features of parkinsonism in humans.MethodsWe assessed lifetime use of pesticides selected by mechanism in a case–control study nested in the Agricultural Health Study (AHS). PD was diagnosed by movement disorders specialists. Controls were a stratified random sample of all AHS participants frequency-matched to cases by age, sex, and state at approximately three controls: one case.ResultsIn 110 PD cases and 358 controls, PD was associated with use of a group of pesticides that inhibit mitochondrial complex I [odds ratio (OR) = 1.7; 95% confidence interval (CI), 1.0–2.8] including rotenone (OR = 2.5; 95% CI, 1.3–4.7) and with use of a group of pesticides that cause oxidative stress (OR = 2.0; 95% CI, 1.2–3.6), including paraquat (OR = 2.5; 95% CI, 1.4–4.7).ConclusionsPD was positively associated with two groups of pesticides defined by mechanisms implicated experimentally—those that impair mitochondrial function and those that increase oxidative stress—supporting a role for these mechanisms in PD pathophysiology.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Tanner, Caroline M. and Kamel, Freya and Ross, G. Webster and Hoppin, Jane A. and Goldman, Samuel M. and Korell, Monica and Marras, Connie and Bhudhikanok, Grace S. and Kasten, Meike and Chade, Anabel R. and et al.}, year={2011}, month={Jun}, pages={866–872} } @article{beard_umbach_hoppin_richards_alavanja_blair_sandler_kamel_2011, title={Suicide and Pesticide Use among Pesticide Applicators and Their Spouses in the Agricultural Health Study}, volume={119}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.1103413}, DOI={10.1289/ehp.1103413}, abstractNote={An association may exist between pesticide exposure and suicide.We sought to evaluate the existence of an association between pesticide use and suicide using data from the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina.Via linkage to state mortality files and the National Death Index, we identified 110 suicides occurring between enrollment in the AHS (from 1993 to 1997) and 31 May 2009, among 81,998 cohort members contributing 1,092,943 person-years of follow-up. The average length of follow-up was 13.3 years. AHS participants provided data on pesticide use and potential confounders via self-administered questionnaires at enrollment. We evaluated several measures of pesticide use: use of any pesticide, ever use of 50 specific pesticides, cumulative lifetime days of use and intensity-adjusted cumulative lifetime days of use of 22 specific pesticides, and ever use of 10 functional and chemical classes of pesticides. We used Cox proportional hazards regression models to estimate adjusted hazard ratios and 95% confidence intervals.After adjusting for age at enrollment, sex, number of children in family, frequency of alcohol consumption during the past 12 months, and smoking status, we found no association between prior pesticide use and suicide in applicators and their spouses. Results were the same for applicators and spouses together or for applicators alone and were consistent across several measures of pesticide use.Our findings do not support an association between moderate pesticide use and suicide.}, number={11}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Beard, John D. and Umbach, David M. and Hoppin, Jane A. and Richards, Marie and Alavanja, Michael C. R. and Blair, Aaron and Sandler, Dale P. and Kamel, Freya}, year={2011}, month={Nov}, pages={1610–1615} } @article{koutros_andreotti_berndt_hughes barry_lubin_hoppin_kamel_sandler_burdette_yuenger_et al._2011, title={Xenobiotic-metabolizing gene variants, pesticide use, and the risk of prostate cancer}, volume={21}, ISSN={1744-6872}, url={http://dx.doi.org/10.1097/FPC.0b013e3283493a57}, DOI={10.1097/FPC.0b013e3283493a57}, abstractNote={To explore associations with prostate cancer and farming, it is important to investigate the relationship between pesticide use and single nucleotide polymorphisms (SNPs) in xenobiotic metabolic enzyme (XME) genes.[corrected] We evaluated pesticide-SNP interactions between 45 pesticides and 1913 XME SNPs with respect to prostrate cancer among 776 cases and 1444 controls in the Agricultural Health Study.We used unconditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Multiplicative SNP-pesticide interactions were calculated using a likelihood ratio test.A positive monotonic interaction was observed between petroleum oil/petroleum distillate use and rs1883633 in the oxidative stress gene glutamate cysteine ligase (GCLC; P interaction=1.0×10(-4)); men carrying at least one variant allele (minor allele) experienced an increased prostate cancer risk (OR=3.7, 95% CI: 1.9-7.3). Among men carrying the variant allele for thioredoxin reductase 2 (TXNRD2) rs4485648, microsomal epoxide hydrolase 1 (EPHX1) rs17309872, or myeloperoxidase (MPO) rs11079344, an increased prostate cancer risk was observed with high, compared with no, petroleum oil/petroleum distillate (OR=1.9, 95% CI: 1.1-3.2, P interaction=0.01; OR=2.1, 95% CI: 1.1-4.0, P interaction=0.01), or terbufos (OR=3.0, 95% CI: 1.5-6.0, P interaction=2.0×10(-3)) use, respectively. No interactions were deemed noteworthy at the false discovery rate=0.20 level; the number of observed interactions in XMEs was comparable with the number expected by chance alone.We observed several pesticide-SNP interactions in oxidative stress and phase I/II enzyme genes and risk of prostate cancer. Additional work is needed to explain the joint contribution of genetic variation in XMEs, pesticide use, and prostate cancer risk.}, number={10}, journal={Pharmacogenetics and Genomics}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Koutros, Stella and Andreotti, Gabriella and Berndt, Sonja I. and Hughes Barry, Kathryn and Lubin, Jay H. and Hoppin, Jane A. and Kamel, Freya and Sandler, Dale P. and Burdette, Laurie A. and Yuenger, Jeffrey and et al.}, year={2011}, month={Oct}, pages={615–623} } @article{koutros_alavanja_lubin_sandler_hoppin_lynch_knott_blair_freeman_2010, title={An Update of Cancer Incidence in the Agricultural Health Study}, volume={52}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e3181f72b7c}, DOI={10.1097/JOM.0b013e3181f72b7c}, abstractNote={Objective: Our objective is to reevaluate cancer incidence among Agricultural Health Study participants. Methods: Standardized incidence ratios (SIRs) and relative standardized ratios were calculated. Results: A significant excess of prostate cancer was seen for private and commercial applicators (SIR = 1.19, 95% CI 1.14, 1.25 and SIR = 1.28, 95% CI = 1.00, 1.61, respectively). Excesses were observed for lip cancer (SIR = 1.97, 95% CI = 1.02, 3.44) and multiple myeloma (SIR = 1.42, 95% CI = 1.00, 1.95) among private applicators from North Carolina and for marginal zone lymphoma among Iowa spouses (SIR = 2.34, 95% CI = 1.21, 4.09). Conclusions: Although lower rates of smoking and increased physical activity probably contribute to the lower overall cancer incidence, agricultural exposures including pesticides, viruses, bacteria, sunlight, and other chemicals may increase risks for specific cancer sites.}, number={11}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Koutros, Stella and Alavanja, Michael C.R. and Lubin, Jay H. and Sandler, Dale P. and Hoppin, Jane A. and Lynch, Charles F. and Knott, Charles and Blair, Aaron and Freeman, Laura E. Beane}, year={2010}, month={Nov}, pages={1098–1105} } @article{andreotti_hou_beane freeman_mahajan_koutros_coble_lubin_blair_hoppin_alavanja_2010, title={Body mass index, agricultural pesticide use, and cancer incidence in the Agricultural Health Study cohort}, volume={21}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-010-9603-9}, DOI={10.1007/s10552-010-9603-9}, abstractNote={Obesity is associated with increased risks of several cancers including colon and female breast. Pesticide use in agricultural populations has also been linked with higher risks of various cancers. However, the interaction between obesity and pesticide use on cancer risk has not been well studied. Using data from the Agricultural Health Study, we examined the association between body mass index (BMI) and the risk of cancer at 17 sites and the interaction between BMI and pesticide use. Pesticide applicators residing in Iowa and North Carolina and their spouses were enrolled between 1993 and 1997 and given a self-administered questionnaire to obtain pesticide use and other information. This analysis included 39,628 men and 28,319 women with height and weight data who were cancer-free at enrollment. Among these participants, 4,432 were diagnosed with cancer between enrollment and 2005 and 64% were overweight or obese. BMI (per 1 kg/m(2)) was positively associated with colon cancer in men (hazard ratio (HR) 1.05, 95% confidence interval (CI) 1.02-1.09) and breast cancer in postmenopausal women (HR 1.03, 95% CI 1.01-1.06). In contrast, BMI was inversely associated with lung cancer in men, with a significant association in ever smokers (HR 0.92, 95% CI 0.88-0.97) and a null association in never smokers. The positive association between BMI and colon cancer in men was significant in those who ever used carbofuran (HR = 1.10, 95% CI 1.04-1.17; p-interaction = 0.04) or metolachlor (HR = 1.09, 95% CI 1.04-1.15; p-interaction = 0.02) but was null in non-users of these pesticides. Among male ever smokers, the inverse association between BMI and lung cancer was significant in non-users of carbofuran (HR = 0.87, 95% CI = 0.82-0.92) but was null in users of carbofuran (p-interaction = 0.02). These findings suggest that certain pesticides may modify the effects of BMI on the risks of colon and lung cancers.}, number={11}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Andreotti, Gabriella and Hou, Lifang and Beane Freeman, Laura E. and Mahajan, Rajeev and Koutros, Stella and Coble, Joseph and Lubin, Jay and Blair, Aaron and Hoppin, Jane A. and Alavanja, Michael}, year={2010}, month={Aug}, pages={1759–1775} } @article{jiao_berrington de gonzalez_hartge_pfeiffer_park_freedman_gail_alavanja_albanes_beane freeman_et al._2010, title={Body mass index, effect modifiers, and risk of pancreatic cancer: a pooled study of seven prospective cohorts}, volume={21}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-010-9558-x}, DOI={10.1007/s10552-010-9558-x}, abstractNote={To investigate whether the positive association of body mass index (BMI, kg/m2) with risk of pancreatic cancer is modified by age, sex, smoking status, physical activity, and history of diabetes. In a pooled analysis of primary data of seven prospective cohorts including 458,070 men and 485,689 women, we identified 2,454 patients with incident pancreatic cancer during an average 6.9 years of follow-up. Cox proportional hazard regression models were used in data analysis. In a random-effects meta-analysis, for every 5 kg/m2 increment in BMI, the summary relative risk (RR) was 1.06 (95% confidence interval (CI) 0.99–1.13) for men and 1.12 (95% CI 1.05–1.19) for women. The aggregate analysis showed that compared with normal weight (BMI: 18.5 to <25), the adjusted RR was 1.13 (95% CI 1.03–1.23) for overweight (BMI: 25 to <30) and 1.19 (95% CI 1.05–1.35) for obesity class I (BMI: 30 to <35). Tests of interactions of BMI effects by other risk factors were not statistically significant. Every 5 kg/m2 increment in BMI was associated with an increased risk of pancreatic cancer among never and former smokers, but not among current smokers (P-interaction = 0.08). The present evidence suggests that a high BMI is an independent risk factor of pancreatic cancer.}, number={8}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Jiao, Li and Berrington de Gonzalez, Amy and Hartge, Patricia and Pfeiffer, Ruth M. and Park, Yikyung and Freedman, D. Michal and Gail, Mitchell H. and Alavanja, Michael C. R. and Albanes, Demetrius and Beane Freeman, Laura E. and et al.}, year={2010}, month={Apr}, pages={1305–1314} } @article{berrington de gonzalez_hartge_cerhan_flint_hannan_macinnis_moore_tobias_anton-culver_freeman_et al._2010, title={Body-Mass Index and Mortality among 1.46 Million White Adults}, volume={363}, ISSN={0028-4793 1533-4406}, url={http://dx.doi.org/10.1056/NEJMoa1000367}, DOI={10.1056/NEJMoa1000367}, abstractNote={A high body-mass index (BMI, the weight in kilograms divided by the square of the height in meters) is associated with increased mortality from cardiovascular disease and certain cancers, but the precise relationship between BMI and all-cause mortality remains uncertain.}, number={23}, journal={New England Journal of Medicine}, publisher={Massachusetts Medical Society}, author={Berrington de Gonzalez, Amy and Hartge, Patricia and Cerhan, James R. and Flint, Alan J. and Hannan, Lindsay and MacInnis, Robert J. and Moore, Steven C. and Tobias, Geoffrey S. and Anton-Culver, Hoda and Freeman, Laura Beane and et al.}, year={2010}, month={Dec}, pages={2211–2219} } @article{christensen_platz_andreotti_blair_hoppin_koutros_lynch_sandler_alavanja_2010, title={Coumaphos Exposure and Incident Cancer among Male Participants in the Agricultural Health Study (AHS)}, volume={118}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.0800446}, DOI={10.1289/ehp.0800446}, abstractNote={BackgroundCoumaphos is an organophosphate livestock insecticide. Previous research in the Agricultural Health Study (AHS) cohort observed a positive association between coumaphos and prostate cancer in men with a family history of prostate cancer.ObjectivesThis study was performed to determine the association between coumaphos and other major cancer sites and to explore the consistency of the association with prostate cancer early (1993–1999) and later (2000–2005) in AHS follow-up.MethodsThis study included 47,822 male licensed pesticide applicators. Incident cases were ascertained by linkage to state cancer registries, and exposure data were collected by enrollment questionnaire. Poisson regression was used to estimate rate ratio (RR) and 95% confidence interval (CI) of cancer for coumaphos exposure controlling for potentially confounding variables.ResultsApproximately 8% of applicators reported use of coumaphos; 8.5% reported a family history of prostate cancer. Cumulative exposure to coumaphos was not associated with cancer risk overall or with any major cancer site including prostate. In men with a family history of prostate cancer, we observed a positive association between ever use of coumaphos and prostate cancer in both early (RR = 2.07; 95% CI, 1.19–3.62, p-interaction = 0.005) and later (RR = 1.46; 95% CI, 0.89–2.40; p-interaction = 0.11) periods of follow-up. Across all years, this association was statistically significant (RR = 1.65; 95% CI, 1.13–2.38; p-interaction = 0.004).ConclusionCoumaphos was not associated with any cancer evaluated here. In men with a family history of disease, there was evidence of an association between coumaphos and prostate cancer, possibly due to genetic susceptibility; however, other explanations, including chance, are plausible.}, number={1}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Christensen, Carol H. and Platz, Elizabeth A. and Andreotti, Gabriella and Blair, Aaron and Hoppin, Jane A. and Koutros, Stella and Lynch, Charles F. and Sandler, Dale P. and Alavanja, Michael C.R.}, year={2010}, month={Jan}, pages={92–96} } @article{romitti_watanabe-galloway_budelier_lynch_puzhankara_wong-gibbons_hoppin_alavanja_2010, title={Identification of Iowa Live Births in the Agricultural Health Study}, volume={65}, ISSN={1933-8244 2154-4700}, url={http://dx.doi.org/10.1080/19338241003730903}, DOI={10.1080/19338241003730903}, abstractNote={ABSTRACT In the Agricultural Health Study, information on participant live births was largely provided by female partners of male private applicators. At the Iowa site, such information was available for 13,599 (42.9%) of 31,707 applicators. To improve identification of live births among Iowa participants, we used a probabilistic and deterministic approach to link available demographic data from 31,707 households and information on live births from 13,599 households with 1,014,916 Iowa birth certificates. Record linkage identified 16,611 (93.7%) of 17,719 reported live births and 17,883 additional live births, most (14,411 or 80.6%) not reported due to nonresponse by female partners. This record linkage produced an expanded cohort of live-born children among Iowa participants, which will facilitate improved study of the effects of agricultural exposures, including pesticides, on selected birth outcomes and childhood disease.}, number={3}, journal={Archives of Environmental & Occupational Health}, publisher={Informa UK Limited}, author={Romitti, Paul A. and Watanabe-Galloway, Shinobu and Budelier, William T. and Lynch, Charles F. and Puzhankara, Soman and Wong-Gibbons, Donna and Hoppin, Jane A. and Alavanja, Michael C. R.}, year={2010}, month={Jul}, pages={154–162} } @article{sathyanarayana_basso_karr_lozano_alavanja_sandler_hoppin_2010, title={Maternal Pesticide Use and Birth Weight in the Agricultural Health Study}, volume={15}, ISSN={1059-924X 1545-0813}, url={http://dx.doi.org/10.1080/10599241003622699}, DOI={10.1080/10599241003622699}, abstractNote={ABSTRACT Studies examining the association between maternal pesticide exposure and low birth weight yield conflicting results. The authors examined the association between maternal pesticide use and birth weight among women in the Agricultural Health Study, a large study of pesticide applicators and their spouses in Iowa and North Carolina. The authors evaluated self-reported pesticide use of 27 individual pesticides in relation to birth weight among 2246 farm women whose most recent singleton birth occurred within 5 years of enrollment (1993–1997). The authors used linear regression models adjusted for site, preterm birth, medical parity, maternal body mass index, height, and smoking. The results showed that mean infant birth weight was 3586 g (± 546 g), and 3% of the infants were low birth weight (<2500 g). First-trimester pesticide-related tasks were not associated with birth weight. Ever use of the pesticide carbaryl was associated with decreased birth weight (−82 g, 95% confidence interval [CI] = −132, −31). This study thus provides limited evidence about pesticide use as a modulator of birth weight. Overall, the authors observed no associations between birth weight and pesticide-related activities during early pregnancy; however, the authors have no data on temporal specificity of individual pesticide exposures prior to or during pregnancy and therefore cannot draw conclusions related to these exposure windows. Given the widespread exposure to pesticide products, additional evaluation of maternal pregnancy exposures at specific time windows and subsequent birth outcomes is warranted.}, number={2}, journal={Journal of Agromedicine}, publisher={Informa UK Limited}, author={Sathyanarayana, Sheela and Basso, Olga and Karr, Catherine J. and Lozano, Paula and Alavanja, Michael and Sandler, Dale P. and Hoppin, Jane A.}, year={2010}, month={Mar}, pages={127–136} } @article{waggoner_kullman_henneberger_umbach_blair_alavanja_kamel_lynch_knott_london_et al._2010, title={Mortality in the Agricultural Health Study, 1993-2007}, volume={173}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwq323}, DOI={10.1093/aje/kwq323}, abstractNote={Comparing agricultural cohorts with the general population is challenging because the general healthiness of farmers may mask potential adverse health effects of farming. Using data from the Agricultural Health Study, a cohort of 89,656 pesticide applicators and their spouses (N = 89, 656) in North Carolina and Iowa, the authors computed standardized mortality ratios (SMRs) comparing deaths from time of the enrollment (1993–1997) through 2007 to state-specific rates. To compensate for the cohort's overall healthiness, relative SMRs were estimated by calculating the SMR for each cause relative to the SMR for all other causes. In 1,198,129 person-years of follow-up, 6,419 deaths were observed. The all-cause mortality rate was less than expected (SMRapplicators = 0.54, 95% confidence interval (CI): 0.52, 0.55; SMRspouses = 0.52, 95% CI: 0.50, 0.55). SMRs for all cancers, heart disease, and diabetes were significantly below 1.0. In contrast, applicators experienced elevated numbers of machine-related deaths (SMR = 4.15, 95% CI: 3.18, 5.31), motor vehicle nontraffic accidents (SMR = 2.80, 95% CI: 1.81, 4.14), and collisions with objects (SMR = 2.12, 95% CI: 1.25, 3.34). In the relative SMR analysis for applicators, the relative mortality ratio was elevated for lymphohematopoietic cancers, melanoma, and digestive system, prostate, kidney, and brain cancers. Among spouses, relative SMRs exceeded 1.0 for lymphohematopoietic cancers and malignancies of the digestive system, brain, breast, and ovary. Unintentional fatal injuries remain an important risk for farmers; mortality ratios from several cancers were elevated relative to other causes.}, number={1}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Waggoner, J. K. and Kullman, G. J. and Henneberger, P. K. and Umbach, D. M. and Blair, A. and Alavanja, M. C. R. and Kamel, F. and Lynch, C. F. and Knott, C. and London, S. J. and et al.}, year={2010}, month={Nov}, pages={71–83} } @article{bonner_williams_rusiecki_blair_beane freeman_hoppin_dosemeci_lubin_sandler_alavanja_2010, title={Occupational exposure to terbufos and the incidence of cancer in the Agricultural Health Study}, volume={21}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-010-9514-9}, DOI={10.1007/s10552-010-9514-9}, abstractNote={Terbufos is the fourth most commonly used organophosphate insecticide (OP) in the United States. Terbufos has not been demonstrated to be carcinogenic in rodents, although non-arsenical insecticides, including OPs, have been associated with excess cancer in epidemiologic studies. We investigated associations between use of terbufos and the incidence of cancer.The Agricultural Health Study is a prospective cohort study of 57,310 licensed pesticide applicators from Iowa and North Carolina. Detailed information about 50 pesticides, including terbufos, and potential confounders was obtained from self-administered questionnaires. Terbufos intensity-weighted lifetime exposure-days were defined as (lifetime exposure-days) x (exposure intensity score). Cases include all first primary cancers diagnosed between enrollment and December 31, 2005. Hazard ratios (HR) and 95% CI were calculated with Cox proportional hazards models, adjusting for potential confounders.Overall cancer risk was slightly increased among terbufos users [HR 1.21 (1.06-1.37)]. Suggestive associations were observed between terbufos use and cancers of the prostate (HR(highest tertile) = 1.21; 95% CI = 0.99-1.47) and lung (HR(middle tertile) = 1.45; 95% CI = 0.95-2.22) and leukemia (HR(middle tertile) = 2.38; 95% CI = 1.35-4.21) and non-Hodgkin's lymphoma (HR(middle tertile) = 1.94; 95% CI = 1.16-3.22), although the exposure-response gradients were non-monotonic and p for trends were not significant.We found suggestive associations between occupational terbufos use and several cancer sites. However, cautious interpretation of these results is warranted by the lack of existing experimental and epidemiologic evidence to support carcinogenic effects of terbufos.}, number={6}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Bonner, Matthew R. and Williams, Brent A. and Rusiecki, Jennifer A. and Blair, Aaron and Beane Freeman, Laura E. and Hoppin, Jane A. and Dosemeci, Mustafa and Lubin, Jay and Sandler, Dale P. and Alavanja, Michael C. R.}, year={2010}, month={Feb}, pages={871–877} } @article{myers_hoppin_olshan_herring_nylander-french_schroeder_sandler_baird_2010, title={Pesticide Exposures and Uterine Fibroid Risk Among Farming Women}, volume={20}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2010.07.047}, DOI={10.1016/j.annepidem.2010.07.047}, abstractNote={Environmental Epigenomics is a developing field to study the epigenetic effect on human health from exposure to environmental factors. Endocrine disrupting chemicals have been detected primarily in pharmaceutical drugs, personal care products, food additives, and food containers. Exposure to endocrine-disrupting chemicals (EDCs) has been associated with a high incidence and prevalence of many endocrine-related disorders in humans. Nevertheless, further evidence is needed to establish a correlation between exposure to EDC and human disorders.Conventional detection of EDCs is based on chemical structure and concentration sample analysis. However, substantial evidence has emerged, suggesting that cell exposure to EDCs leads to epigenetic changes, independently of its chemical structure with non-monotonic low-dose responses.Consequently, a paradigm shift in toxicology assessment of EDCs is proposed based on a comprehensive review of analytical techniques used to evaluate the epigenetic effects. Fundamental insights reported elsewhere are compared in order to establish DNA methylation analysis as a viable method for assessing endocrine disruptors beyond the conventional study approach of chemical structure and concentration analysis.}, number={9}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Myers, S.L. and Hoppin, J.A. and Olshan, A.F. and Herring, A.H. and Nylander-French, L. and Schroeder, J.C. and Sandler, D.P. and Baird, D.D.}, year={2010}, month={Sep}, pages={707} } @article{koutros_beane freeman_berndt_andreotti_lubin_sandler_hoppin_yu_li_burdette_et al._2010, title={Pesticide Use Modifies the Association Between Genetic Variants on Chromosome 8q24 and Prostate Cancer}, volume={70}, ISSN={0008-5472 1538-7445}, url={http://dx.doi.org/10.1158/0008-5472.CAN-10-1078}, DOI={10.1158/0008-5472.CAN-10-1078}, abstractNote={Genome-wide association studies have identified 8q24 region variants as risk factors for prostate cancer. In the Agricultural Health Study, a prospective study of licensed pesticide applicators, we observed increased prostate cancer risk with specific pesticide use among those with a family history of prostate cancer. Thus, we evaluated the interaction among pesticide use, 8q24 variants, and prostate cancer risk. The authors estimated odds ratios (OR) and 95% confidence intervals (95% CI) for interactions among 211 8q24 variants, 49 pesticides, and prostate cancer risk in 776 cases and 1,444 controls. The ORs for a previously identified variant, rs4242382, and prostate cancer increased significantly (P<0.05) with exposure to the organophosphate insecticide fonofos, after correction for multiple testing, with per allele ORnonexposed of 1.17 (95% CI, 0.93-1.48), per allele OR(low) of 1.30 (95% CI, 0.75-2.27), and per allele ORhigh of 4.46 (95% CI, 2.17-9.17; P-interaction=0.002, adjusted P-interaction=0.02). A similar effect modification was observed for three other organophosphate insecticides (coumaphos, terbufos, and phorate) and one pyrethroid insecticide (permethrin). Among ever users of fonofos, subjects with three or four risk alleles at rs7837328 and rs4242382 had approximately three times the risk of prostate cancer (OR, 3.14; 95% CI, 1.41-7.00) compared with subjects who had zero risk alleles and never used fonofos. We observed a significant interaction among variants on chromosome 8q24, pesticide use, and risk of prostate cancer. Insecticides, particularly organophosphates, were the strongest modifiers of risk, although the biological mechanism is unclear. This is the first report of effect modification between 8q24 and an environmental exposure on prostate cancer risk.}, number={22}, journal={Cancer Research}, publisher={American Association for Cancer Research (AACR)}, author={Koutros, S. and Beane Freeman, L. E. and Berndt, S. I. and Andreotti, G. and Lubin, J. H. and Sandler, D. P. and Hoppin, J. A. and Yu, K. and Li, Q. and Burdette, L. A. and et al.}, year={2010}, month={Oct}, pages={9224–9233} } @article{dayton_sandler_blair_alavanja_beane freeman_hoppin_2010, title={Pesticide Use and Myocardial Infarction Incidence Among Farm Women in the Agricultural Health Study}, volume={52}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e3181e66d25}, DOI={10.1097/JOM.0b013e3181e66d25}, abstractNote={Objective: To evaluate the relationship between pesticide use and myocardial infarction (MI) among farm women. Background: Little is known about the potential association between pesticide use and cardiovascular outcomes. Methods: We used logistic regression to evaluate pesticide use and self-reported incident nonfatal MI among women in the Agricultural Health Study. Results: Of those MI-free at enrollment (n = 22,425), 168 reported an MI after enrollment. We saw no association with pesticide use overall. Six of 27 individual pesticides evaluated were significantly associated with nonfatal MI, including chlorpyrifos, coumaphos, carbofuran, metalaxyl, pendimethalin, and trifluralin, which all had odds ratios >1.7. These chemicals were used by <10% of the cases, and their use was correlated, making it difficult to attribute the risk elevation to a specific pesticide. Conclusion: Pesticides may contribute to MI risk among farm women.}, number={7}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Dayton, Shile B. and Sandler, Dale P. and Blair, Aaron and Alavanja, Michael and Beane Freeman, Laura E. and Hoppin, Jane A.}, year={2010}, month={Jul}, pages={693–697} } @article{goldner_sandler_yu_hoppin_kamel_levan_2010, title={Pesticide Use and Thyroid Disease Among Women in the Agricultural Health Study}, volume={171}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwp404}, DOI={10.1093/aje/kwp404}, abstractNote={Thyroid disease is common, and evidence of an association between organochlorine exposure and thyroid disease is increasing. The authors examined the cross-sectional association between ever use of organochlorines and risk of hypothyroidism and hyperthyroidism among female spouses (n = 16,529) in Iowa and North Carolina enrolled in the Agricultural Health Study in 1993-1997. They also assessed risk of thyroid disease in relation to ever use of herbicides, insecticides, fungicides, and fumigants. Prevalence of self-reported clinically diagnosed thyroid disease was 12.5%, and prevalence of hypothyroidism and hyperthyroidism was 6.9% and 2.1%, respectively. There was an increased odds of hypothyroidism with ever use of organochlorine insecticides (adjusted odds ratio (OR(adj)) = 1.2 (95% confidence interval (CI): 1.0, 1.6) and fungicides (OR(adj) = 1.4 (95% CI: 1.1, 1.8) but no association with ever use of herbicides, fumigants, organophosphates, pyrethroids, or carbamates. Specifically, ever use of the organochlorine chlordane (OR(adj) = 1.3 (95% CI: 0.99, 1.7), the fungicides benomyl (OR(adj) = 3.1 (95% CI: 1.9, 5.1) and maneb/mancozeb (OR(adj) = 2.2 (95% CI: 1.5, 3.3), and the herbicide paraquat (OR(adj) = 1.8 (95% CI: 1.1, 2.8) was significantly associated with hypothyroidism. Maneb/mancozeb was the only pesticide associated with both hyperthyroidism (OR(adj) = 2.3 (95% CI: 1.2, 4.4) and hypothyroidism. These data support a role of organochlorines, in addition to fungicides, in the etiology of thyroid disease among female spouses enrolled in the Agricultural Health Study.}, number={4}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Goldner, W. S. and Sandler, D. P. and Yu, F. and Hoppin, J. A. and Kamel, F. and LeVan, T. D.}, year={2010}, month={Jan}, pages={455–464} } @article{slager_simpson_levan_poole_sandler_hoppin_2010, title={Rhinitis Associated with Pesticide Use Among Private Pesticide Applicators in the Agricultural Health Study}, volume={73}, ISSN={1528-7394 1087-2620}, url={http://dx.doi.org/10.1080/15287394.2010.497443}, DOI={10.1080/15287394.2010.497443}, abstractNote={Farmers commonly experience rhinitis but the risk factors are not well characterized. The aim of this study was to analyze cross-sectional data on rhinitis in the past year and pesticide use from 21,958 Iowa and North Carolina farmers in the Agricultural Health Study, enrolled 1993–1997, to evaluate pesticide predictors of rhinitis. Polytomous and logistic regression models were used to assess association between pesticide use and rhinitis while controlling for demographics and farm-related exposures. Sixty-seven percent of farmers reported current rhinitis and 39% reported 3 or more rhinitis episodes. The herbicides glyphosate [odds ratio (OR) = 1.09, 95% confidence interval (95% CI) = 1.05–1.13] and petroleum oil (OR = 1.12, 95% CI = 1.05–1.19) were associated with current rhinitis and increased rhinitis episodes. Of the insecticides, four organophosphates (chlorpyrifos, diazinon, dichlorvos, and malathion), carbaryl, and use of permethrin on animals were predictors of current rhinitis. Diazinon was significant in the overall polytomous model and was associated with an elevated OR of 13+ rhinitis episodes (13+ episodes OR = 1.23, 95% CI = 1.09–1.38). The fungicide captan was also a significant predictor of rhinitis. Use of petroleum oil, use of malathion, use of permethrin, and use of the herbicide metolachlor were significant in exposure-response polytomous models. Specific pesticides may contribute to rhinitis in farmers; agricultural activities did not explain these findings.}, number={20}, journal={Journal of Toxicology and Environmental Health, Part A}, publisher={Informa UK Limited}, author={Slager, Rebecca E. and Simpson, Sean L. and LeVan, Tricia D. and Poole, Jill A. and Sandler, Dale P. and Hoppin, Jane A.}, year={2010}, month={Aug}, pages={1382–1393} } @article{andreotti_freeman_hou_coble_rusiecki_hoppin_silverman_alavanja_2009, title={Agricultural pesticide use and pancreatic cancer risk in the Agricultural Health Study Cohort}, volume={124}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.24185}, DOI={10.1002/ijc.24185}, abstractNote={Abstract Pancreatic cancer is a rapidly fatal disease that has been linked with pesticide use. Previous studies have reported excess risks of pancreatic cancer with organochlorines such as DDT, however, many other commonly used pesticides have not been examined. To further examine the potential associations between the use of a number of pesticides and pancreatic cancer, we conducted a case‐control analysis in the Agricultural Health Study, one of the largest prospective cohorts with over 89,000 participants including pesticide applicators and their spouses in Iowa and North Carolina. This analysis included 93 incident pancreatic cancer cases (64 applicators, 29 spouses) and 82,503 cancer‐free controls who completed an enrollment questionnaire providing detailed pesticide use, demographic and lifestyle information. Ever use of 24 pesticides and intensity‐weighted lifetime days [(lifetime exposure days) × (exposure intensity score)] of 13 pesticides was assessed. Risk estimates were calculated using unconditional logistic regression controlling for age, smoking, and diabetes. Among pesticide applicators, 2 herbicides (EPTC and pendimethalin) of the 13 pesticides examined for intensity‐weighted lifetime use showed a statistically significant exposure‐response association with pancreatic cancer. Applicators in the top half of lifetime pendimethalin use had a 3.0‐fold (95% CI 1.3–7.2, p ‐trend = 0.01) risk compared with never users, and those in the top half of lifetime EPTC use had a 2.56‐fold (95% CI = 1.1–5.4, p ‐trend = 0.01) risk compared with never users. Organochlorines were not associated with an excess risk of pancreatic cancer in this study. These findings suggest that herbicides, particularly pendimethalin and EPTC, may be associated with pancreatic cancer. © 2008 Wiley‐Liss, Inc.}, number={10}, journal={International Journal of Cancer}, publisher={Wiley}, author={Andreotti, Gabriella and Freeman, Laura E. Beane and Hou, Lifang and Coble, Joseph and Rusiecki, Jennifer and Hoppin, Jane A. and Silverman, Debra T. and Alavanja, Michael C.R.}, year={2009}, month={May}, pages={2495–2500} } @article{thomas_dosemeci_coble_hoppin_sheldon_chapa_croghan_jones_knott_lynch_et al._2009, title={Assessment of a pesticide exposure intensity algorithm in the agricultural health study}, volume={20}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2009.54}, DOI={10.1038/jes.2009.54}, abstractNote={The accuracy of the exposure assessment is a critical factor in epidemiological investigations of pesticide exposures and health in agricultural populations. However, few studies have been conducted to evaluate questionnaire-based exposure metrics. The Agricultural Health Study (AHS) is a prospective cohort study of pesticide applicators who provided detailed questionnaire information on their use of specific pesticides. A field study was conducted for a subset of the applicators enrolled in the AHS to assess a pesticide exposure algorithm through comparison of algorithm intensity scores with measured exposures. Pre- and post-application urinary biomarker measurements were made for 2,4-D (n=69) and chlorpyrifos (n=17) applicators. Dermal patch, hand wipe, and personal air samples were also collected. Intensity scores were calculated using information from technician observations and an interviewer-administered questionnaire. Correlations between observer and questionnaire intensity scores were high (Spearman's r=0.92 and 0.84 for 2,4-D and chlorpyrifos, respectively). Intensity scores from questionnaires for individual applications were significantly correlated with post-application urinary concentrations for both 2,4-D (r=0.42, P<0.001) and chlorpyrifos (r=0.53, P=0.035) applicators. Significant correlations were also found between intensity scores and estimated hand loading, estimated body loading, and air concentrations for 2,4-D applicators (r-values 0.28–0.50, P-values<0.025). Correlations between intensity scores and dermal and air measures were generally lower for chlorpyrifos applicators using granular products. A linear regression model indicated that the algorithm factors for individual applications explained 24% of the variability in post-application urinary 2,4-D concentration, which increased to 60% when the pre-application urine concentration was included. The results of the measurements support the use of the algorithm for estimating questionnaire-based exposure intensities in the AHS for liquid pesticide products. Refinement of the algorithm may be possible using the results from this and other measurement studies.}, number={6}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Thomas, Kent W and Dosemeci, Mustafa and Coble, Joseph B and Hoppin, Jane A and Sheldon, Linda S and Chapa, Guadalupe and Croghan, Carry W and Jones, Paul A and Knott, Charles E and Lynch, Charles F and et al.}, year={2009}, month={Nov}, pages={559–569} } @article{park_kang_beane-freeman_blair_hoppin_sandler_lynch_knott_gwak_alavanja_2009, title={Cancer Incidence Among Paraquat Exposed Applicators in the Agricultural Health Study: A Prospective Cohort Study}, volume={15}, ISSN={1077-3525 2049-3967}, url={http://dx.doi.org/10.1179/oeh.2009.15.3.274}, DOI={10.1179/oeh.2009.15.3.274}, abstractNote={AbstractAbstractParaquat (1,1′-dimethyl-4, 4′-bipyridinium dichloride) is a nonselective herbicide that is extremely toxic after acute exposure. It was once widely used in North America and is still used in some countries, including the United States. Although there is little firm evidence that paraquat is a carcinogen, previous studies have suggested a potential relationship with some cancers. This prospective cohort study was performed to evaluate the association between lifetime paraquat exposure and cancer incidence among licensed pesticide applicators with 9.1 years of median follow-up. The lifetime ever-use of paraquat was evaluated in 56,224 subjects at baseline and exposure-response relationship was evaluated in 24,667 subjects (44%) who provided detailed information on total life-time paraquat exposure in a second questionnaire. Among the total subjects, the risk for non-Hodgkin's lymphoma (NHL) in the exposed group was marginally elevated (Relative risk [RR], 1.47; 95% confidence interval [CI], 0.97–2.23) compared to the non-exposed group. However, among the 24,667 applicators who supplied total life-time exposure days, the highest tertile of lifetime exposure-days (LE) and intensity-weighted lifetime exposure-days (IWLE) was not significantly associated with NHL risk (RR, 1.57; 95%CI, 0.57–4.23 for LE; RR, 1.42; 95%CI, 0.40–4.71 for IWLE, respectively) and there was no significant exposure-response trend (p-trend > 0.1). There was some suggestion of a possible link between paraquat exposure and NHL risk in humans, but the inconsistency in exposure level trend suggests that this could be a chance finding.Keywords: PARAQUATCANCER INCIDENCENON-HODGKIN'S LYMPHOMAAGRICULTURAL HEALTH STUDY}, number={3}, journal={International Journal of Occupational and Environmental Health}, publisher={Informa UK Limited}, author={Park, Sue K. and Kang, Daehee and Beane-Freeman, Laura and Blair, Aaron and Hoppin, Jane A. and Sandler, Dale P. and Lynch, Charles F. and Knott, Charles and Gwak, Jin and Alavanja, Michael}, year={2009}, month={Jul}, pages={274–281} } @article{hughes_koutros_coble_lubin_beane freeman_sandler_hoppin_ma_zheng_alavanja_2009, title={Cancer Incidence Among Pesticide Applicators Exposed to Methyl Bromide in the AHS}, volume={19}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2009.07.055}, DOI={10.1016/j.annepidem.2009.07.055}, number={9}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Hughes, K.J. and Koutros, S. and Coble, J. and Lubin, J. and Beane Freeman, L.E. and Sandler, D.P. and Hoppin, J.A. and Ma, X. and Zheng, T. and Alavanja, M.C.R.}, year={2009}, month={Sep}, pages={662–663} } @article{rusiecki_patel_koutros_beane-freeman_landgren_bonner_coble_lubin_blair_hoppin_et al._2009, title={Cancer Incidence among Pesticide Applicators Exposed to Permethrin in the Agricultural Health Study}, volume={117}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.11318}, DOI={10.1289/ehp.11318}, abstractNote={BackgroundPermethrin is a synthetic pyrethroid insecticide widely used in agriculture, in public health, and in many U.S. homes and gardens.ObjectiveIn this study we evaluated the incidence of cancer among pesticide applicators exposed to permethrin in the Agricultural Health Study (AHS).MethodsA total of 49,093 pesticide applicators were included in this analysis of the AHS, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed in 1993–1997. Average length of follow-up since applicator enrollment in the cohort was 9.14 years. We used two permethrin exposure metrics: a) lifetime days applicators personally mixed or applied permethrin and b) intensity-weighted lifetime days (lifetime days weighted by estimated intensity of exposure). We used Poisson regression analysis to estimate relative risks (RRs) and 95% confidence intervals (CIs) for malignancies by tertiles of exposure.ResultsWe found no associations between permethrin and all malignant neoplasms combined, or between permethrin and melanoma, non-Hodgkin lymphoma, leukemia, or cancers of the colon, rectum, lung, or prostate. We found elevated and statistically significant risks for multiple myeloma in the highest tertiles of both lifetime exposure-days (RR = 5.72; 95% CI, 2.76–11.87) and intensity-weighted lifetime exposure-days (RR = 5.01; 95% CI, 2.41–10.42), compared with applicators reporting they never used permethrin; these results are based on only 15 exposed cases. These findings were similar across a variety of alternative exposure metrics, exposure categories, and reference groups.ConclusionsThis study found no association with most cancers analyzed. Although the suggested association with multiple myeloma was based on a small number of cases, it warrants further evaluation.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Rusiecki, Jennifer A. and Patel, Rahulkumar and Koutros, Stella and Beane-Freeman, Laura and Landgren, Ola and Bonner, Matthew R. and Coble, Joseph and Lubin, Jay and Blair, Aaron and Hoppin, Jane A. and et al.}, year={2009}, month={Apr}, pages={581–586} } @article{lynch_mahajan_beane freeman_hoppin_alavanja_2009, title={Cancer incidence among pesticide applicators exposed to butylate in the Agricultural Health Study (AHS)}, volume={109}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2009.06.006}, DOI={10.1016/j.envres.2009.06.006}, abstractNote={Although limited, epidemiologic studies suggest possible associations between butylate use and cancer risk, specifically prostate cancer and non-Hodgkin lymphoma (NHL). We examined butylate use and cancer risk more broadly in the AHS, a cohort of licensed pesticide applicators in Iowa and North Carolina. Pesticide use information was collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CI). Two exposure metrics were used: lifetime exposure days (LD) and intensity-weighted lifetime exposure days (IWLD). We used two referent groups: unexposed to butylate and the lowest butylate usage category. This analysis included 19,655 applicators with complete butylate use information; 5297 applicators were exposed to butylate, making this the largest study of butylate to date. The mean follow-up time since enrollment was 9 years. Prostate cancer risk was significantly elevated among applicators in the highest LD category in both referent groups (low-exposed referent: RRLD=2.09, 95% CI=1.27–3.44). We observed a significantly elevated joint effect of prostate cancer family history and high butylate usage across both exposure metrics and both referent groups (low-exposed referent: RRLD=2.00, 95% CI=1.07–3.74), and a non-significant, elevated interaction between butylate use and prostate cancer family history, similar to a previous AHS finding. Statistically significant increased risks and exposure–response trends were seen for all lymphohematopoietic cancers (AL) and NHL for both exposure metrics and referent groups (low-exposed referent: AL:RRLD=2.27, 95% CI=1.18–4.37; NHL: RRLD=3.44, 95% CI=1.29–9.21). Our analysis did not find meaningful associations for other cancers analyzed. Further study is warranted for AL, NHL and prostate cancers.}, number={7}, journal={Environmental Research}, publisher={Elsevier BV}, author={Lynch, Shannon M. and Mahajan, Rajeev and Beane Freeman, Laura E. and Hoppin, Jane A. and Alavanja, Michael C.R.}, year={2009}, month={Oct}, pages={860–868} } @article{montgomery_kamel_hoppin_freeman_alavanja_sandler_2009, title={Effects of self-reported health conditions and pesticide exposures on probability of follow-up in a prospective cohort study}, volume={53}, ISSN={0271-3586 1097-0274}, url={http://dx.doi.org/10.1002/ajim.20789}, DOI={10.1002/ajim.20789}, abstractNote={Abstract Background We investigated the potential for selection bias due to non‐participation in the follow‐up of a large prospective cohort study. Methods Licensed pesticide applicators (52,395 private; 4,916 commercial) in the Agricultural Health Study provided demographic, health, and pesticide exposure information at enrollment (1993–1997) and in a 5‐year follow‐up telephone interview. Factors associated with non‐participation in the follow‐up were identified using multiple logistic regression. Potential for selection bias was evaluated by comparing exposure–disease associations between the entire cohort and the follow‐up subset. Results Sixty‐six percent of private and 60% of commercial applicators completed the follow‐up interview. Private and commercial applicators who did not complete the follow‐up reported at enrollment younger age, less education, lower body mass index, poorer health behaviors but fewer health conditions, and lower pesticide use. Estimates of exposure–disease associations calculated with and without non‐participants did not indicate strong selection bias. Conclusions Differences between non‐participants and participants in the follow‐up interview were generally small, and we did not find significant evidence of selection bias. However, the extent of bias may depend on the specific exposure and outcome under study. Am. J. Ind. Med. 53:486–496, 2010. © 2009 Wiley‐Liss, Inc.}, number={5}, journal={American Journal of Industrial Medicine}, publisher={Wiley}, author={Montgomery, Martha P. and Kamel, Freya and Hoppin, Jane A. and Freeman, Laura E. Beane and Alavanja, Michael C.R. and Sandler, Dale P.}, year={2009}, pages={n/a-n/a} } @article{koutros_lynch_ma_lee_hoppin_christensen_andreotti_freeman_rusiecki_hou_et al._2009, title={Heterocyclic aromatic amine pesticide use and human cancer risk: Results from the U.S. Agricultural Health Study}, volume={124}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.24020}, DOI={10.1002/ijc.24020}, abstractNote={Abstract Imazethapyr, a heterocyclic aromatic amine, is a widely used crop herbicide first registered for use in the United States in 1989. We evaluated cancer incidence among imazethapyr‐exposed pesticide applicators enrolled in the Agricultural Health Study (AHS). The AHS is a prospective cohort of 57,311 licensed pesticide applicators in the U.S., enrolled from 1993–1997. Among the 49,398 licensed pesticide applicators eligible for analysis, 20,646 applicators reported use of imazethapyr and 2,907 incident cancers developed through 2004. Imazethapyr exposure was classified by intensity‐weighted lifetime exposure days calculated as [years of use × days per year × intensity level]. Poisson regression analysis was used to evaluate the relationship between imazethapyr exposure and cancer incidence. We found significant trends in risk with increasing lifetime exposure for bladder cancer ( p for trend 0.01) and colon cancer ( p for trend 0.02). Rate ratios (RRs) were increased by 137% for bladder cancer and 78% for colon cancer when the highest exposed were compared to the nonexposed. The excess risk for colon cancer was limited to proximal cancers, (RR = 2.73, 95% confidence intervals 1.42, 5.25, p for trend 0.001). No association was observed for prostate, lung, rectum, kidney, oral, pancreas, lymphohematopoietic cancers or melanoma. These findings provide new evidence that exposure to aromatic amine pesticides may be an overlooked exposure in the etiology of bladder and colon cancer. The use of imazethapyr and other imidazolinone compounds should continue to be evaluated for potential risk to humans. Published 2008 Wiley‐Liss, Inc.}, number={5}, journal={International Journal of Cancer}, publisher={Wiley}, author={Koutros, Stella and Lynch, Charles F. and Ma, Xiaomei and Lee, Won Jin and Hoppin, Jane A. and Christensen, Carol H. and Andreotti, Gabriella and Freeman, Laura Beane and Rusiecki, Jennifer A. and Hou, Lifang and et al.}, year={2009}, month={Mar}, pages={1206–1212} } @article{ye_pierik_angerer_meltzer_jaddoe_tiemeier_hoppin_longnecker_2009, title={Levels of metabolites of organophosphate pesticides, phthalates, and bisphenol A in pooled urine specimens from pregnant women participating in the Norwegian Mother and Child Cohort Study (MoBa)}, volume={212}, ISSN={1438-4639}, url={http://dx.doi.org/10.1016/j.ijheh.2009.03.004}, DOI={10.1016/j.ijheh.2009.03.004}, abstractNote={Concerns about reproductive and developmental health risks of exposure to organophosphate (OP) pesticides, phthalates, and bisphenol A (BPA) among the general population are increasing. Six dialkyl phosphate (DAP) metabolites, 3,5,6-trichloro-2-pyridinol (TCPy), BPA, and fourteen phthalate metabolites were measured in 10 pooled urine samples representing 110 pregnant women who participated in the Norwegian Mother and Child Birth Cohort (MoBa) study in 2004. Daily intakes were estimated from urinary data and compared with reference doses (RfDs) and daily tolerable intakes (TDIs). The MoBa women had a higher mean BPA concentration (4.50 microg/L) than the pregnant women in the Generation R Study (Generation R) in the Netherlands and the National Health and Nutrition Examination Survey (NHANES) in the United States. The mean concentration of total DAP metabolites (24.20 microg/L) in MoBa women was higher than that in NHANES women but lower than that in Generation R women. The diethyl phthalate metabolite mono-ethyl phthalate (MEP) was the dominant phthalate metabolite in all three studies, with the mean concentrations of greater than 300 microg/L. The MoBa and Generation R women had higher mean concentrations of mono-n-butyl phthalate (MnBP) and mono-isobutyl phthalate (MiBP) than the NHANES women. The estimated average daily intakes of BPA, chlorpyrifos/chlorpyrifos-methyl and phthalates in MoBa (and the other two studies) were below the RfDs and TDIs. The higher levels of metabolites in the MoBa participants may have been from intake via pesticide residues in food (organophosphates), consumption of canned food, especially fish/seafood (BPA), and use of personal care products (selected phthalates).}, number={5}, journal={International Journal of Hygiene and Environmental Health}, publisher={Elsevier BV}, author={Ye, Xibiao and Pierik, Frank H. and Angerer, Jürgen and Meltzer, Helle Margrete and Jaddoe, Vincent W.V. and Tiemeier, Henning and Hoppin, Jane A. and Longnecker, Matthew P.}, year={2009}, month={Sep}, pages={481–491} } @article{bronstein_carvey_chen_cory-slechta_dimonte_duda_english_goldman_grate_hansen_et al._2009, title={Meeting Report: Consensus Statement—Parkinson’s Disease and the Environment: Collaborative on Health and the Environment and Parkinson’s Action Network (CHE PAN) Conference 26–28 June 2007}, volume={117}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.11702}, DOI={10.1289/ehp.11702}, abstractNote={BackgroundParkinson’s disease (PD) is the second most common neurodegenerative disorder. People with PD, their families, scientists, health care providers, and the general public are increasingly interested in identifying environmental contributors to PD risk.MethodsIn June 2007, a multidisciplinary group of experts gathered in Sunnyvale, California, USA, to assess what is known about the contribution of environmental factors to PD.ResultsWe describe the conclusions around which they came to consensus with respect to environmental contributors to PD risk. We conclude with a brief summary of research needs.ConclusionsPD is a complex disorder, and multiple different pathogenic pathways and mechanisms can ultimately lead to PD. Within the individual there are many determinants of PD risk, and within populations, the causes of PD are heterogeneous. Although rare recognized genetic mutations are sufficient to cause PD, these account for < 10% of PD in the U.S. population, and incomplete penetrance suggests that environmental factors may be involved. Indeed, interplay among environmental factors and genetic makeup likely influences the risk of developing PD. There is a need for further understanding of how risk factors interact, and studying PD is likely to increase understanding of other neurodegenerative disorders.}, number={1}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Bronstein, Jeff and Carvey, Paul and Chen, Honglei and Cory-Slechta, Deborah and DiMonte, Donato and Duda, John and English, Paul and Goldman, Samuel and Grate, Stephen and Hansen, Johnni and et al.}, year={2009}, month={Jan}, pages={117–121} } @article{delancey_alavanja_coble_blair_hoppin_austin_beane freeman_2009, title={Occupational Exposure to Metribuzin and the Incidence of Cancer in the Agricultural Health Study}, volume={19}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2008.12.018}, DOI={10.1016/j.annepidem.2008.12.018}, abstractNote={Little is known about the potential carcinogenicity of the triazinone herbicide metribuzin. We evaluated the association between metribuzin use and cancer risk in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Applicators (N = 23,072) provided information on metribuzin use on a self-administered questionnaire at enrollment (1993–1997). Among metribuzin users (n = 8,504), there were 554 incident cancer cases. We used multivariable Poisson regression to evaluate potential associations between metribuzin use and cancer incidence by using two quantitative exposure metrics, lifetime days and intensity-weighted lifetime days. Using intensity-weighted lifetime days, the rate ratio (RR) and 95% confidence interval (CI) for the highest exposed tertile for lymphohematopoietic malignancies were 2.09 (95% CI: 0.99–4.29), p trend = 0.02 and 2.42 (95% CI: 0.82–7.19), p trend = 0.08 for leukemia. For non-Hodgkin lymphoma, the RR was 2.64 (95% CI: 0.76–9.11), p trend = 0.13 for lifetime days and 2.52 (95% CI: 0.66–9.59), p trend = 0.13 for intensity-weighted lifetime days. Patterns of association were similar for both exposure metrics, but associations were generally weaker than for intensity-weighted days. The results from this study suggest a potential association between metribuzin use and certain lymphohematopoietic malignancies; however, having not been observed previously, caution should be used in interpretation.}, number={6}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Delancey, John Oliver L. and Alavanja, Michael C.R. and Coble, Joseph and Blair, Aaron and Hoppin, Jane A. and Austin, Harland D. and Beane Freeman, Laura E.}, year={2009}, month={Jun}, pages={388–395} } @article{slager_levan_poole_sandler_hoppin_2009, title={Occupational Risk Factors for Rhinitis Among Farmers in the Agricultural Health Study}, volume={123}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2008.12.1029}, DOI={10.1016/j.jaci.2008.12.1029}, number={2}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Slager, R.E. and LeVan, T.D. and Poole, J.A. and Sandler, D.P. and Hoppin, J.A.}, year={2009}, month={Feb}, pages={S266–S266} } @article{saldana_basso_baird_hoppin_weinberg_blair_alavanja_sandler_2009, title={Pesticide Exposure and Hypertensive Disorders During Pregnancy}, volume={117}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.0900672}, DOI={10.1289/ehp.0900672}, abstractNote={Hypertensive disorders of pregnancy, including pregnancy-induced hypertension (PIH) and preeclampsia (PE), complicate 2-8% of pregnancies. Few studies have examined environmental risk factors in relation to these conditions.Our goal was to examine whether pesticide exposure during pregnancy was associated with hypertensive disorders of pregnancy.We analyzed self-reported data from 11,274 wives of farmers enrolled in the Agricultural Health Study (AHS) between 1993 and 1997. Using logistic regression models, we estimated the adjusted odds ratios (AORs) for PIH and PE associated with pesticide-related activities during the first trimester of pregnancy.First-trimester residential and agricultural activities with potential exposure to pesticides were associated with both PIH [residential AOR = 1.27; 95% confidence interval (CI), 1.02-1.60; agricultural AOR = 1.60; 95% CI, 1.05-2.45] and PE (residential AOR = 1.32; 95% CI, 1.02-1.70; agricultural AOR = 2.07; 95% CI, 1.34-3.21).Exposure to pesticides during pregnancy may increase the risk of hypertensive disorders of pregnancy. Laboratory research may provide insights into relationships between pesticide exposure and hypertensive diseases of pregnancy.}, number={9}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Saldana, Tina M. and Basso, Olga and Baird, Donna D. and Hoppin, Jane A. and Weinberg, Clarice R. and Blair, Aaron and Alavanja, Michael C.R. and Sandler, Dale P.}, year={2009}, month={Sep}, pages={1393–1396} } @article{landgren_kyle_hoppin_beane freeman_cerhan_katzmann_rajkumar_alavanja_2009, title={Pesticide exposure and risk of monoclonal gammopathy of undetermined significance in the Agricultural Health Study}, volume={113}, ISSN={0006-4971 1528-0020}, url={http://dx.doi.org/10.1182/blood-2009-02-203471}, DOI={10.1182/blood-2009-02-203471}, abstractNote={Pesticides are associated with excess risk of multiple myeloma, albeit inconclusively. We included 678 men (30-94 years) from a well-characterized prospective cohort of restricted-use pesticide applicators to assess the risk of monoclonal gammopathy of undetermined significance (MGUS). Serum samples from all subjects were analyzed by electrophoresis performed on agarose gel; samples with a discrete or localized band were subjected to immunofixation. Age-adjusted prevalence estimates of MGUS were compared with MGUS prevalence in 9469 men from Minnesota. Associations between pesticide exposures and MGUS prevalence were assessed by logistic regression models adjusted for age and education level. Among study participants older than 50 years (n = 555), 38 were found to have MGUS, yielding a prevalence of 6.8% (95% CI, 5.0%-9.3%). Compared with men from Minnesota, the age-adjusted prevalence of MGUS was 1.9-fold (95% CI, 1.3- to 2.7-fold) higher among male pesticide applicators. Among applicators, a 5.6-fold (95% CI, 1.9- to 16.6-fold), 3.9-fold (95% CI, 1.5- to 10.0-fold), and 2.4-fold (95% CI, 1.1- to 5.3-fold) increased risk of MGUS prevalence was observed among users of the chlorinated insecticide dieldrin, the fumigant mixture carbon-tetrachloride/carbon disulfide, and the fungicide chlorothalonil, respectively. In summary, the prevalence of MGUS among pesticide applicators was twice that in a population-based sample of men from Minnesota, adding support to the hypothesis that specific pesticides are causatively linked to myelomagenesis.}, number={25}, journal={Blood}, publisher={American Society of Hematology}, author={Landgren, O. and Kyle, R. A. and Hoppin, J. A. and Beane Freeman, L. E. and Cerhan, J. R. and Katzmann, J. A. and Rajkumar, S. V. and Alavanja, M. C.}, year={2009}, month={Apr}, pages={6386–6391} } @article{hoppin_umbach_london_henneberger_kullman_coble_alavanja_beane freeman_sandler_2009, title={Pesticide use and adult-onset asthma among male farmers in the Agricultural Health Study}, volume={34}, ISSN={0903-1936 1399-3003}, url={http://dx.doi.org/10.1183/09031936.00005509}, DOI={10.1183/09031936.00005509}, abstractNote={Although specific pesticides have been associated with wheeze in farmers, little is known about pesticides and asthma. Data from 19,704 male farmers in the Agricultural Health Study were used to evaluate lifetime use of 48 pesticides and prevalent adult-onset asthma, defined as doctor-diagnosed asthma after the age of 20 yrs. Asthma cases were categorised as allergic (n = 127) and nonallergic (n = 314) based on their history of eczema or hay fever. Polytomous logistic regression, controlling for age, state, smoking and body mass, was used to assess pesticide associations. High pesticide exposure events were associated with a doubling of both allergic and nonallergic asthma. For ever-use, 12 individual pesticides were associated with allergic asthma and four with nonallergic asthma. For allergic asthma, coumaphos (OR 2.34; 95% CI 1.49–3.70), heptachlor (OR 2.01; 95% CI 1.30–3.11), parathion (OR 2.05; 95% CI 1.21–3.46), 80/20 mix (carbon tetrachloride/carbon disulfide) (OR 2.15; 95% CI 1.23–3.76) and ethylene dibromide (OR 2.07; 95% CI 1.02–4.20) all showed ORs of >2.0 and significant exposure–response trends. For nonallergic asthma, DDT (dichlorodiphenyltrichloroethane) showed the strongest association (OR 1.41; 95% CI 1.09–1.84), but with little evidence of increasing asthma with increasing use. Current animal handling and farm activities did not confound these results. There was little evidence that allergy alone was driving these associations. In conclusion, pesticides may be an overlooked contributor to asthma risk among farmers.}, number={6}, journal={European Respiratory Journal}, publisher={European Respiratory Society (ERS)}, author={Hoppin, J. A. and Umbach, D. M. and London, S. J. and Henneberger, P. K. and Kullman, G. J. and Coble, J. and Alavanja, M. C. R. and Beane Freeman, L. E. and Sandler, D. P.}, year={2009}, month={Jun}, pages={1296–1303} } @article{mills_blair_freeman_sandler_hoppin_2009, title={Pesticides and Myocardial Infarction Incidence and Mortality Among Male Pesticide Applicators in the Agricultural Health Study}, volume={170}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwp214}, DOI={10.1093/aje/kwp214}, abstractNote={Acute organophosphate and carbamate pesticide poisonings result in adverse cardiac outcomes. The cardiac effects of chronic low-level pesticide exposure have not been studied. The authors analyzed self-reported lifetime use of pesticides reported at enrollment (1993–1997) and myocardial infarction mortality through 2006 and self-reported nonfatal myocardial infarction through 2003 among male pesticide applicators in the Agricultural Health Study. Using proportional hazard models, the authors estimated the association between lifetime use of 49 pesticides and fatal and nonfatal myocardial infarction. There were 476 deaths from myocardial infarction among 54,069 men enrolled in the study and 839 nonfatal myocardial infarctions among the 32,024 participants who completed the follow-up interview. Fatal and nonfatal myocardial infarctions were associated with commonly reported risk factors, including age and smoking. There was little evidence of an association between having used pesticides, individually or by class, and myocardial infarction mortality (e.g., insecticide hazard ratio (HR) = 0.91, 95% confidence interval (CI): 0.67, 1.24; herbicide HR = 0.74, 95% CI: 0.49, 1.10) or nonfatal myocardial infarction incidence (e.g., insecticide HR = 0.85, 95% CI: 0.66, 1.09; herbicide HR = 0.91, 95% CI: 0.61, 1.36). There was no evidence of a dose response with any pesticide measure. In a population with low risk for myocardial infarction, the authors observed little evidence of increased risk of myocardial infarction mortality or nonfatal myocardial infarction associated with the occupational use of pesticides.}, number={7}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Mills, Katherine T. and Blair, Aaron and Freeman, Laura E. Beane and Sandler, Dale P. and Hoppin, Jane A.}, year={2009}, month={Aug}, pages={892–900} } @article{slager_poole_levan_sandler_alavanja_hoppin_2009, title={Rhinitis associated with pesticide exposure among commercial pesticide applicators in the Agricultural Health Study}, volume={66}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.2008.041798}, DOI={10.1136/oem.2008.041798}, abstractNote={Rhinitis is common, but the risk factors are not well described. To investigate the association between current rhinitis and pesticide use, we used data from 2245 Iowa commercial pesticide applicators in the Agricultural Health Study.Using logistic regression models adjusted for age, education and growing up on a farm, we evaluated the association between current rhinitis and 34 pesticides used in the past year.74% of commercial pesticide applicators reported at least one episode of rhinitis in the past year (current rhinitis). Five pesticides used in the past year were significantly positively associated with current rhinitis: the herbicides 2,4-D, glyphosate and petroleum oil, the insecticide diazinon and the fungicide benomyl. The association for 2,4-D and glyphosate was limited to individuals who used both in the past year (OR 1.42, 95% CI 1.14 to 1.77). Both petroleum oil and diazinon showed consistent evidence of an association with rhinitis, based on both current use and exposure-response models. We saw no evidence of confounding by common agricultural rhinitis triggers such as handling grain or hay.Exposure to pesticides may increase the risk of rhinitis.}, number={11}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Slager, R E and Poole, J A and LeVan, T D and Sandler, D P and Alavanja, M C R and Hoppin, J A}, year={2009}, month={Mar}, pages={718–724} } @article{thomas_dosemeci_hoppin_sheldon_croghan_gordon_jones_reynolds_raymer_akland_et al._2009, title={Urinary biomarker, dermal, and air measurement results for 2,4-D and chlorpyrifos farm applicators in the Agricultural Health Study}, volume={20}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2009.6}, DOI={10.1038/jes.2009.6}, abstractNote={A subset of private pesticide applicators in the Agricultural Health Study (AHS) epidemiological cohort was monitored around the time of their agricultural use of 2,4-dichlorophenoxyacetic acid (2,4-D) and O,O-diethyl-O-3,5,6-trichloro-2-pyridyl phosphorothioate (chlorpyrifos) to assess exposure levels and potential determinants of exposure. Measurements included pre- and post-application urine samples, and patch, hand wipe, and personal air samples. Boom spray or hand spray application methods were used by applicators for 2,4-D products. Chlorpyrifos products were applied using spray applications and in-furrow application of granular products. Geometric mean (GM) values for 69 2,4-D applicators were 7.8 and 25 μg/l in pre- and post-application urine, respectively (P<0.05 for difference); 0.39 mg for estimated hand loading; 2.9 mg for estimated body loading; and 0.37 μg/m3 for concentration in personal air. Significant correlations were found between all media for 2,4-D. GM values for 17 chlorpyrifos applicators were 11 μg/l in both pre- and post-application urine for the 3,5,6-trichloro-2-pyridinol metabolite, 0.28 mg for body loading, and 0.49 μg/m3 for air concentration. Only 53% of the chlorpyrifos applicators had measurable hand loading results; their median hand loading being 0.02 mg. Factors associated with differences in 2,4-D measurements included application method and glove use, and, for hand spray applicators, use of adjuvants, equipment repair, duration of use, and contact with treated vegetation. Spray applications of liquid chlorpyrifos products were associated with higher measurements than in-furrow granular product applications. This study provides information on exposures and possible exposure determinants for several application methods commonly used by farmers in the cohort and will provide information to assess and refine exposure classification in the AHS. Results may also be of use in pesticide safety education for reducing exposures to pesticide applicators.}, number={2}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Thomas, Kent W and Dosemeci, Mustafa and Hoppin, Jane A and Sheldon, Linda S and Croghan, Carry W and Gordon, Sydney M and Jones, Martin L and Reynolds, Stephen J and Raymer, James H and Akland, Gerald G and et al.}, year={2009}, month={Feb}, pages={119–134} } @article{nepomnaschy_baird_weinberg_hoppin_longnecker_wilcox_2009, title={Within-person variability in urinary bisphenol A concentrations: Measurements from specimens after long-term frozen storage}, volume={109}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2009.04.004}, DOI={10.1016/j.envres.2009.04.004}, abstractNote={Bisphenol A (BPA) is an estrogenic contaminant of food and water associated with adverse developmental effects in laboratory animals. BPA has recently been linked to morbidity in adult humans, but studies of developmental effects in humans are methodologically more difficult. The ability to measure BPA in urine samples after long-term storage could aid in such studies. Because the half-life of BPA is <6 h, a single measurement would be useful only if the environmental exposure is relatively constant over weeks or months. Our aims were to evaluate the stability of BPA in specimens after 22–24 years of storage and to measure within-person temporal variability in urinary BPA. We measured total BPA concentration by mass spectrometry in first-morning urine samples from 60 premenopausal women. We selected from each woman's stored daily collections three urine samples approximately 2 and 4 weeks apart. Samples were selected from both the follicular and luteal phases of the menstrual cycle to assess cycle effects. Temporal variability was assessed with mixed model regression and correlations. BPA levels had an inter-quartile range from 1.1 to 3.1 ng/mg creatinine, slightly higher than levels in specimens from NHANES collected 3–11 years later. The Spearman correlation was approximately 0.5 for samples 2 weeks apart and 0.3 for samples 4 weeks apart. Menstrual cycle phase did not influence levels. BPA tended to increase during the three-year collection period, but not significantly. The similar distribution to NHANES samples and correlation of BPA levels taken at 2-week intervals provide indirect evidence that BPA is relatively stable during long-term freezer storage. The correlations indicate generally stable exposures over periods of weeks. These findings suggest that developmental effects of BPA exposure could be investigated with measurements from stored urine.}, number={6}, journal={Environmental Research}, publisher={Elsevier BV}, author={Nepomnaschy, Pablo A. and Baird, Donna Day and Weinberg, Clarice R. and Hoppin, Jane A. and Longnecker, Matthew P. and Wilcox, Allen J.}, year={2009}, month={Aug}, pages={734–737} } @article{baird_saldana_nepomnaschy_hoppin_longnecker_weinberg_wilcox_2009, title={Within-person variability in urinary phthalate metabolite concentrations: measurements from specimens after long-term frozen storage}, volume={20}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/jes.2009.17}, DOI={10.1038/jes.2009.17}, abstractNote={Laboratory studies show that exposure to phthalates during development can cause adverse effects, especially for males. Studies in humans would be facilitated by collection of urine during pregnancy, long-term storage, and measurement of phthalate metabolites at the time that offspring health is assessed. Our aims were to measure urinary phthalate metabolites after long-term freezer storage, to use those measurements to evaluate within-woman variability over 2- and 4-week intervals, and to determine whether the phases of the menstrual cycle affect metabolite levels. Samples were selected from daily first-morning urine specimens collected by 60 women and stored frozen since 1983-1985. Three specimens per woman were selected at approximately 2-week intervals to include both follicular and luteal phase samples. Seven metabolites of five phthalates were measured by mass spectrometry. Statistical analyses were conducted with correlation, mixed model regression, and the Wilcoxon signed rank test. Creatinine-corrected urinary phthalate metabolite concentrations measured in samples after long-term storage tended to have a similar right-skewed distribution, though with somewhat higher concentrations than those reported for recently collected US samples. The concentrations of three metabolites of di(2-ethylhexyl)phthalate in the same specimen were very highly correlated (Pearson r=0.85-0.97). Reproducibility over a 4-week interval was moderate for the metabolites of diethyl phthalate and benzylbutyl phthalate (intraclass correlation coefficients, ICCs, 0.48 and 0.53, respectively), whereas five other metabolites had lower ICCs (0.21-0.37). Menstrual phase was not related to metabolite concentrations. Although the same samples have not been measured both before and after long-term storage, results suggest that the measurement of phthalate metabolites after long-term sample storage yield generally similar distributions and temporal reliability as those reported for recently collected specimens. These findings support the use of stored urine specimens collected during the relevant stage of human pregnancy to investigate the influence of phthalate exposures on later outcomes.}, number={2}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Baird, Donna Day and Saldana, Tina M and Nepomnaschy, Pablo A and Hoppin, Jane A and Longnecker, Matthew P and Weinberg, Clarice R and Wilcox, Allen J}, year={2009}, month={Mar}, pages={169–175} } @article{longnecker_smith_kissling_hoppin_butenhoff_decker_ehresman_ellefson_flaherty_gardner_et al._2008, title={An interlaboratory study of perfluorinated alkyl compound levels in human plasma}, volume={107}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2008.01.005}, DOI={10.1016/j.envres.2008.01.005}, abstractNote={We conducted an interlaboratory study which differed from the typical study of this type because of its emphasis on comparing intralaboratory variability in results. We sent specimens to six laboratories experienced in the analysis of perfluorinated alkyl compounds in blood matrices and that use stringent procedures to control and assure accuracy and precision. Each received an identical set of 60 plasma specimens that were analyzed in six completely independent batches. Split specimens were included so that within- and between-batch coefficients of variation could be calculated. All laboratories used liquid chromatography–tandem mass spectrometry (LC–MS/MS). The concentrations of perfluorooctanesulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorohexanesulfonate (PFHxS) measured in the specimens in general showed a high level of agreement, although in some cases the agreement was only moderate. The average within- and between-batch coefficient of variation for PFOS was 9.1% and 9.3%; for PFOA was 14.5% and 14.5%; and for PFHxS was 14.5% and 17.0%. The recent availability of labeled internal standards, among other advances, has facilitated improvement in the accuracy and precision of the assays. Considering the degree of between-subject variation in levels among people in background-exposed populations, the results indicate that biomarker-based epidemiologic studies of associations with health could have reasonable precision.}, number={2}, journal={Environmental Research}, publisher={Elsevier BV}, author={Longnecker, Matthew P. and Smith, Cynthia S. and Kissling, Grace E. and Hoppin, Jane A. and Butenhoff, John L. and Decker, Emily and Ehresman, David J. and Ellefson, Mark E. and Flaherty, John and Gardner, Michael S. and et al.}, year={2008}, month={Jun}, pages={152–159} } @article{koutros_lynch_ma_lee_hoppin_christensen_andreotti_freeman_rusiecki_hou_et al._2008, title={Aromatic Amine Pesticide Use And Human Cancer Risk: Results From The U.S. Agricultural Health Study}, volume={18}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2008.08.043}, DOI={10.1016/j.annepidem.2008.08.043}, number={9}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Koutros, S and Lynch, C.F. and Ma, X. and Lee, W.J. and Hoppin, J.A. and Christensen, C.H. and Andreotti, G. and Freeman, L Beane and Rusiecki, J.A. and Hou, L. and et al.}, year={2008}, month={Sep}, pages={720} } @article{greenburg_rusiecki_koutros_dosemeci_patel_hines_hoppin_alavanja_2008, title={Cancer incidence among pesticide applicators exposed to captan in the Agricultural Health Study}, volume={19}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-008-9187-9}, DOI={10.1007/s10552-008-9187-9}, abstractNote={{"Label"=>"OBJECTIVE", "NlmCategory"=>"OBJECTIVE"} Captan is a widely used antifungal pesticide whose potential to cause cancer in humans is uncertain. {"Label"=>"METHODS", "NlmCategory"=>"METHODS"} We evaluated the incidence of cancer among pesticide applicators exposed to captan in the Agricultural Health Study. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered enrollment questionnaires completed between 1993 and 1997. {"Label"=>"RESULTS", "NlmCategory"=>"RESULTS"} Of the 48,986 applicators enrolled 4,383 (9%) had applied captan. Median follow-up time was 9.14 years. Poisson regression analysis was used to estimate relative risks (RR) for cancer subtypes by tertiles of captan exposure. We investigated risk for all cancers combined and sites of cancer for which at least 15 cases occurred among captan-exposed applicators. These sites included cancers of the prostate, lung, and colon, blood-related cancers, and colorectal cancers. During follow-up 2,912 incident primary cases of cancer were identified. No association between the highest tertile of captan exposure (>67.375 intensity-weighted days) and development of all cancers (RR = 0.89; 95% CI, 0.71-1.13) or cancer of any specific site was observed. {"Label"=>"CONCLUSION", "NlmCategory"=>"CONCLUSIONS"} Although our study is limited by low numbers of observed cancer cases and follow-up time of 9.14 years, it does not provide evidence of an increased risk for the development of cancer at the investigated sites.}, number={10}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Greenburg, David L. and Rusiecki, Jennifer and Koutros, Stella and Dosemeci, Mustafa and Patel, Rahulkumar and Hines, Cynthia J. and Hoppin, Jane A. and Alavanja, Michael C. R.}, year={2008}, month={Jun}, pages={1401–1407} } @article{kang_park_beane-freeman_lynch_knott_sandler_hoppin_dosemeci_coble_lubin_et al._2008, title={Cancer incidence among pesticide applicators exposed to trifluralin in the Agricultural Health Study}, volume={107}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2008.01.010}, DOI={10.1016/j.envres.2008.01.010}, abstractNote={Trifluralin, 2,6-dinitro-N,N-dipropyl-4-trifluoromethylaniline, is a 2,6-dinitro herbicide widely used to control annual grasses and broadleaf weeds in agricultural settings. The association between trifluralin use and common cancer incidence was evaluated among 50,127 private and commercial pesticide applicators in the Agricultural Health Study (AHS), a prospective cohort study of licensed pesticide applicators and their spouses in Iowa and North Carolina. Poisson regression was used to examine internal dose-response relationships, while controlling for important lifestyle factors and other agricultural exposures. Two metrics of exposure (lifetime days and intensity-weighted lifetime days) were used in exposure-response analyses with non-exposed applicators, as well as applicators in the lowest tertile of exposure, as reference groups. Incident cancers were identified through state tumor registries from enrollment in 1993 through 2002. Trifluralin exposure was not associated with cancer incidence overall among 51% of private and commercial applicators (n=25,712) who had used trifluralin. However, there was an excess of colon cancer in the exposure category of higher half of highest tertile (rate ratios (RR) of 1.76 (95% CI=1.05-2.95) using the non-exposed as a referent and 1.93 (95% CI=1.08-3.45) using those with the lowest tertile of exposure as the referent). There was also a non-significantly elevated risk for kidney cancer and bladder cancer in the highest exposure group, although only the kidney cancer finding was consistent across exposure metrics. Although there was a possible link between trifluralin exposure and colon cancer, small numbers and inconsistencies in dose-response and subgroup analyses indicate that this may be a chance finding.}, number={2}, journal={Environmental Research}, publisher={Elsevier BV}, author={Kang, Daehee and Park, Sue Kyung and Beane-Freeman, Laura and Lynch, Charles F. and Knott, Charles E. and Sandler, Dale P. and Hoppin, Jane A. and Dosemeci, Mustafa and Coble, Joseph and Lubin, Jay and et al.}, year={2008}, month={Jun}, pages={271–276} } @article{mozzachio_rusiecki_hoppin_mahajan_patel_beane-freeman_alavanja_2008, title={Chlorothalonil exposure and cancer incidence among pesticide applicator participants in the agricultural health study}, volume={108}, ISSN={0013-9351}, url={http://dx.doi.org/10.1016/j.envres.2008.07.018}, DOI={10.1016/j.envres.2008.07.018}, abstractNote={Chlorothalonil is a broad spectrum, non-systemic fungicide widely used to control diseases affecting over 50 fruit, vegetable, and agricultural crops. Despite its extensive use for over 30 years, little is known about the potential human carcinogenicity associated with the routine application of chlorothalonil. Rodent studies have shown evidence of renal tubular carcinomas and adenomas. We explored cancer incidence with chlorothalonil exposure using data from the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Licensed private and commercial pesticide applicators were recruited into this study from 1993 to 1997. Detailed information regarding pesticide use was obtained via self-administered questionnaires. Cancer incidence was followed through December 31, 2004. Chlorothalonil exposure was classified by lifetime exposure days and intensity-weighted lifetime exposure days, and then categorized into tertiles. The intensity-weighted lifetime exposure days metric was calculated based on a complex algorithm which includes pesticide application methods among other factors. This may increase or decrease exposure. Of the 47,625 pesticide applicators included in this analysis, 3657 applicators reported using chlorothalonil with a median of 3.5 application days per year. Chlorothalonil was not associated with overall cancer incidence, nor did we find any association with colon, lung, and prostate cancers—the only cancers for which we had sufficient numbers to explore associations. We did not find any strong evidence for an association between chlorothalonil and the cancers investigated. Although animal studies have suggested renal cancer may be associated with chlorothalonil, we had insufficient data to evaluate this cancer.}, number={3}, journal={Environmental Research}, publisher={Elsevier BV}, author={Mozzachio, Alicia M. and Rusiecki, Jennifer A. and Hoppin, Jane A. and Mahajan, Rajeev and Patel, Rahulkumar and Beane-Freeman, Laura and Alavanja, Michael CR}, year={2008}, month={Nov}, pages={400–403} } @article{beseler_stallones_hoppin_alavanja_blair_keefe_kamel_2008, title={Depression and Pesticide Exposures among Private Pesticide Applicators Enrolled in the Agricultural Health Study}, volume={116}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.11091}, DOI={10.1289/ehp.11091}, abstractNote={BackgroundWe evaluated the relationship between diagnosed depression and pesticide exposure using information from private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997 in Iowa and North Carolina.MethodsThere were 534 cases who self-reported a physician-diagnosed depression and 17,051 controls who reported never having been diagnosed with depression and did not feel depressed more than once a week in the past year. Lifetime pesticide exposure was categorized in three mutually exclusive groups: low (< 226 days, the reference group), intermediate (226–752 days), and high (> 752 days). Two additional measures represented acute high-intensity pesticide exposures: an unusually high pesticide exposure event (HPEE) and physician-diagnosed pesticide poisoning. Logistic regression analyses were performed relating pesticide exposure to depression.ResultsAfter adjusting for state, age, education, marital status, doctor visits, alcohol use, smoking, solvent exposure, not currently having crops or animals, and ever working a job off the farm, pesticide poisoning was more strongly associated with depression [odds ratio (OR) = 2.57; 95% confidence interval (CI), 1.74–3.79] than intermediate (OR = 1.07; 95% CI, 0.87–1.31) or high (OR = 1.11; 95% CI, 0.87–1.42) cumulative exposure or an HPEE (OR = 1.65; 95% CI, 1.33–2.05). In analysis of a subgroup without a history of acute poisoning, high cumulative exposure was significantly associated with depression (OR = 1.54; 95% CI, 1.16–2.04).ConclusionThese findings suggest that both acute high-intensity and cumulative pesticide exposure may contribute to depression in pesticide applicators. Our study is unique in reporting that depression is also associated with chronic pesticide exposure in the absence of a physician-diagnosed poisoning.}, number={12}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Beseler, Cheryl L. and Stallones, Lorann and Hoppin, Jane A. and Alavanja, Michael C.R. and Blair, Aaron and Keefe, Thomas and Kamel, Freya}, year={2008}, month={Dec}, pages={1713–1719} } @article{paltiel_rønningen_meltzer_baker_hoppin_2008, title={Evaluation of Freeze–Thaw Cycles on Stored Plasma in the Biobank of the Norwegian Mother and Child Cohort Study}, volume={6}, ISSN={1538-344X 1557-8119}, url={http://dx.doi.org/10.1089/cpt.2008.0012}, DOI={10.1089/cpt.2008.0012}, abstractNote={In many cohort studies, biological specimens are being stored without specific plans for analyses. In the Norwegian Mother and Child Cohort Study biological specimens (DNA, plasma, and whole blood) are stored on 96-well plates and as a result may undergo multiple freeze–thaw cycles. To explore the impact of multiple freeze–thaw cycles on chemical constituents, we conducted a quality control study using pooled EDTA-plasma. Over a 2-year period, samples stored at −80°C were subjected up to 100 freeze–thaw cycles. Specimens were analyzed in triplicate for sodium, cholesterol, triglycerides, vitamin E, aspartate aminotransferase (AST), and free-fatty acids. We assessed the percent change of analyte concentration from the values for the first freeze–thaw cycle, because this is the baseline for all stored specimens. With the exception of free fatty acids, there was little change over the first 10 freeze–thaw cycles. A majority of analytes showed no significant changes until 30 freeze–thaw cycles. After 30 freeze–thaw cycles, the largest percent change was observed for free fatty acids (+32%), AST (+21%), and triglycerides (−19%). Human plasma can go through several freeze–thaw cycles before analysis without influencing sample integrity for the selected analytes.}, number={3}, journal={Cell Preservation Technology}, publisher={Mary Ann Liebert Inc}, author={Paltiel, Liv and Rønningen, Kjersti S. and Meltzer, Helle M. and Baker, Susan V. and Hoppin, Jane A.}, year={2008}, month={Sep}, pages={223–229} } @article{crawford_hoppin_alavanja_blair_sandler_kamel_2008, title={Hearing Loss Among Licensed Pesticide Applicators in the Agricultural Health Study}, volume={50}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e31816a8caf}, DOI={10.1097/JOM.0b013e31816a8caf}, abstractNote={Objective: We evaluated self-reported hearing loss and pesticide exposure in licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993 to 1997 in Iowa and North Carolina. Methods: Among 14,229 white male applicators in 1999 to 2003, 4926 reported hearing loss (35%). Logistic regression was performed with adjustment for state, age, and noise, solvents, and metals. We classified pesticides by lifetime days of use. Results: Compared with no exposure, the odds ratio (95% confidence interval) for the highest quartile of exposure was 1.19 (1.04 to 1.35) for insecticides and 1.17 (1.03 to 1.31) for organophosphate insecticides. Odds of hearing loss were elevated for high pesticide exposure events (1.38, 1.25 to 1.54), pesticide-related doctor visits (1.38, 1.17 to 1.62) or hospitalization (1.81, 1.25 to 2.62), and diagnosed pesticide poisoning (1.75, 1.36 to 2.26). Conclusions: Although control for exposure to noise or other neurotoxicants was limited, this study extends previous reports suggesting that organophosphate exposure increases risk of hearing loss.}, number={7}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Crawford, John Mac and Hoppin, Jane A. and Alavanja, Michael C. R. and Blair, Aaron and Sandler, Dale P. and Kamel, Freya}, year={2008}, month={Jul}, pages={817–826} } @article{koutros_cross_sandler_hoppin_ma_zheng_alavanja_sinha_2008, title={Meat and Meat Mutagens and Risk of Prostate Cancer in the Agricultural Health Study}, volume={17}, ISSN={1055-9965 1538-7755}, url={http://dx.doi.org/10.1158/1055-9965.EPI-07-0392}, DOI={10.1158/1055-9965.EPI-07-0392}, abstractNote={Meats cooked at high temperatures, such as pan-frying or grilling, are a source of carcinogenic heterocyclic amines and polycyclic aromatic hydrocarbons. We prospectively examined the association between meat types, meat cooking methods, meat doneness, and meat mutagens and the risk for prostate cancer in the Agricultural Health Study. We estimated relative risks and 95% confidence intervals (95% CI) for prostate cancer using Cox proportional hazards regression using age as the underlying time metric and adjusting for state of residence, race, smoking status, and family history of prostate cancer. During 197,017 person-years of follow-up, we observed 668 incident prostate cancer cases (613 of these were diagnosed after the first year of follow-up and 140 were advanced cases) among 23,080 men with complete dietary data. We found no association between meat type or specific cooking method and prostate cancer risk. However, intake of well or very well done total meat was associated with a 1.26-fold increased risk of incident prostate cancer (95% CI, 1.02-1.54) and a 1.97-fold increased risk of advanced disease (95% CI, 1.26-3.08) when the highest tertile was compared with the lowest. Risks for the two heterocyclic amines 2-amino-3,4,8-trimethylimidazo-[4,5-f]quinoxaline and 2-amino-3,8-dimethylimidazo-[4,5-b]quinoxaline were of borderline significance for incident disease [1.24 (95% CI, 0.96-1.59) and 1.20 (95% CI, 0.93-1.55), respectively] when the highest quintile was compared with the lowest. In conclusion, well and very well done meat was associated with an increased risk for prostate cancer in this cohort.}, number={1}, journal={Cancer Epidemiology Biomarkers & Prevention}, publisher={American Association for Cancer Research (AACR)}, author={Koutros, S. and Cross, A. J. and Sandler, D. P. and Hoppin, J. A. and Ma, X. and Zheng, T. and Alavanja, M. C.R. and Sinha, R.}, year={2008}, month={Jan}, pages={80–87} } @article{slager_poole_levan_hoppin_2008, title={Occupational Rhinitis is Associated with Pesticide Exposure Among Commercial Pesticide Applicators in the Agricultural Health Study}, volume={121}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2007.12.926}, DOI={10.1016/j.jaci.2007.12.926}, abstractNote={Workplace-induced occupational rhinitis is becoming increasingly important, but is often under-diagnosed. As pesticide exposures have previously been associated with respiratory tract symptoms, the aim of this study was to examine the association between pesticide exposures and rhinitis in routinely exposed workers. We analyzed data on current rhinitis and pesticide use among 2245 Iowa commercial pesticide applicators in the Agricultural Health Study. At enrollment (1993-7), participants provided detailed information on current use of 40 pesticides as well as demographic, smoking and medical history and potential agricultural exposures. We developed a logistic regression model controlling for age, education status, and growing up on a farm to investigate self-reported current rhinitis (defined as at least one episode of rhinitis in the past year). 1664 workers (74%) reported at least one episode of rhinitis in the past year. Use of the following 7 pesticides in the past year (of 40 tested) was significantly associated with current rhinitis: 2,4-D (Odds Ratio (OR) = 1.37, 95% Confidence Interval (CI) = 1.10, 1.65), glyphosate (OR = 1.33, 95% CI = 1.09, 1.62), pendamethalin (OR = 1.28. 95% CI = 1.01, 1.61), petroleum oil (OR = 1.77, 95% CI = 1.27, 2.46), diazinon (OR = 1.87, 95% CI = 1.25, 2.80), benomyl (OR = 2.37, 95% CI = 1.12, 5.03), and aluminum phosphide (OR = 1.62, 95% CI = 1.01, 2.60). Exclusion of asthmatics did not alter these results. Exposure to specific pesticides may increase the risk of occupational rhinitis.}, number={2}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Slager, R and Poole, J and Levan, T and Hoppin, J}, year={2008}, month={Feb}, pages={S234–S234} } @article{hoppin_umbach_london_henneberger_kullman_alavanja_sandler_2008, title={Pesticides and Atopic and Nonatopic Asthma among Farm Women in the Agricultural Health Study}, volume={177}, ISSN={1073-449X 1535-4970}, url={http://dx.doi.org/10.1164/rccm.200706-821OC}, DOI={10.1164/rccm.200706-821OC}, abstractNote={Risk factors for asthma among farm women are understudied.We evaluated pesticide and other occupational exposures as risk factors for adult-onset asthma.Studying 25,814 farm women in the Agricultural Health Study, we used self-reported history of doctor-diagnosed asthma with or without eczema and/or hay fever to create two case groups: patients with atopic asthma and those with nonatopic asthma. We assessed disease-exposure associations with polytomous logistic regression.At enrollment (1993-1997), 702 women (2.7%) reported a doctor's diagnosis of asthma after age 19 years (282 atopic, 420 nonatopic). Growing up on a farm (61% of all farm women) was protective for atopic asthma (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.43-0.70) and, to a lesser extent, for nonatopic asthma (OR, 0.83; 95%CI, 0.68-1.02; P value for difference = 0.008). Pesticide use was almost exclusively associated with atopic asthma. Any use of pesticides on the farm was associated only with atopic asthma (OR, 1.46; 95% CI, 1.14-1.87). This association with pesticides was strongest among women who had grown up on a farm. Women who grew up on farms and did not apply pesticides had the lowest overall risk of atopic asthma (OR, 0.41; 95% CI, 0.27-0.62) compared with women who neither grew up on farms nor applied pesticides. A total of 7 of 16 insecticides, 2 of 11 herbicides, and 1 of 4 fungicides were significantly associated with atopic asthma; only permethrin use on crops was associated with nonatopic asthma.These findings suggest that pesticides may contribute to atopic asthma, but not nonatopic asthma, among farm women.}, number={1}, journal={American Journal of Respiratory and Critical Care Medicine}, publisher={American Thoracic Society}, author={Hoppin, Jane A. and Umbach, David M. and London, Stephanie J. and Henneberger, Paul K. and Kullman, Greg J. and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2008}, month={Jan}, pages={11–18} } @article{van bemmel_visvanathan_beane freeman_coble_hoppin_alavanja_2008, title={S -Ethyl- N,N -dipropylthiocarbamate Exposure and Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study: A Prospective Cohort}, volume={116}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.11371}, DOI={10.1289/ehp.11371}, abstractNote={The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled between 1993 and 1997. EPTC (S-ethyl-N,N-dipropylthiocarbamate) is a thiocarbamate herbicide used in every region of the United States. The U.S. Environmental Protection Agency reports that EPTC is most likely not a human carcinogen; however, the previous epidemiologic data on EPTC exposure and cancer risk were limited.}, number={11}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={van Bemmel, Dana M. and Visvanathan, Kala and Beane Freeman, Laura E. and Coble, Joseph and Hoppin, Jane A. and Alavanja, Michael C.R.}, year={2008}, month={Nov}, pages={1541–1546} } @article{maclehose_dunson_herring_hoppin_2007, title={Bayesian Methods for Highly Correlated Exposure Data}, volume={18}, ISSN={1044-3983}, url={http://dx.doi.org/10.1097/01.ede.0000256320.30737.c0}, DOI={10.1097/01.ede.0000256320.30737.c0}, abstractNote={Studies that include individuals with multiple highly correlated exposures are common in epidemiology. Because standard maximum likelihood techniques often fail to converge in such instances, hierarchical regression methods have seen increasing use. Bayesian hierarchical regression places prior distributions on exposure-specific regression coefficients to stabilize estimation and incorporate prior knowledge, if available. A common parametric approach in epidemiology is to treat the prior mean and variance as fixed constants. An alternative parametric approach is to place distributions on the prior mean and variance to allow the data to help inform their values. As a more flexible semiparametric option, one can place an unknown distribution on the coefficients that simultaneously clusters exposures into groups using a Dirichlet process prior. We also present a semiparametric model with a variable-selection prior to allow clustering of coefficients at 0. We compare these 4 hierarchical regression methods and demonstrate their application in an example estimating the association of herbicides with retinal degeneration among wives of pesticide applicators.}, number={2}, journal={Epidemiology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={MacLehose, Richard F. and Dunson, David B. and Herring, Amy H. and Hoppin, Jane A.}, year={2007}, month={Mar}, pages={199–207} } @article{mahajan_blair_coble_lynch_hoppin_sandler_alavanja_2007, title={Carbaryl exposure and incident cancer in the Agricultural Health Study}, volume={121}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.22836}, DOI={10.1002/ijc.22836}, abstractNote={Carbaryl is a carbamate insecticide with a broad spectrum of uses in agricultural, commercial and household settings. It has previously been linked with non-Hodgkin lymphoma (NHL) but studies of cancer risk in humans are limited. We examined occupational carbaryl use and risk of all cancers in the Agricultural Health Study, a prospective study of a cohort of pesticide applicators in North Carolina and Iowa. This analysis included 21,416 subjects (1,291 cases) enrolled from 1993-1997 and followed for cancer incidence through 2003. Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders. Carbaryl was not associated with cancer risk overall. Relative to subjects who never used carbaryl, melanoma risk was elevated with >175 lifetime exposure-days (RR = 4.11; 95%CI, 1.33-12.75; p-trend = 0.07), >10 years of use (RR = 3.19; 95%CI, 1.28-7.92; p-trend = 0.04), or >or=10 days of use per year (RR = 5.50; 95%CI, 2.19-13.84; p-trend < 0.001). Risk remained after adjusting for sunlight exposure. Although not significant, there appeared to be a trend of decreasing prostate cancer risk with increasing level of exposure. A small increase in NHL risk was observed using some, but not all, exposure measures. No associations were observed with other examined cancer sites. Because the observed results were not hypothesized a priori and because of limited study of their biological plausibility, they should be interpreted with caution.}, number={8}, journal={International Journal of Cancer}, publisher={Wiley}, author={Mahajan, Rajeev and Blair, Aaron and Coble, Joseph and Lynch, Charles F. and Hoppin, Jane A. and Sandler, Dale P. and Alavanja, Michael C.R.}, year={2007}, pages={1799–1805} } @article{valcin_henneberger_kullman_umbach_london_alavanja_sandler_hoppin_2007, title={Chronic Bronchitis Among Nonsmoking Farm Women in the Agricultural Health Study}, volume={49}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/JOM.0b013e3180577768}, DOI={10.1097/JOM.0b013e3180577768}, abstractNote={Objective: The purpose of this study was to examine agricultural risk factors for chronic bronchitis among nonsmoking farm women. Methods: We used self-reported enrollment data from the 21,541 nonsmoking women in the Agricultural Health Study to evaluate occupational risk factors for prevalent chronic bronchitis among farm women. Odds ratios (ORs) for chronic bronchitis for occupational exposures were adjusted for age, state, and related agricultural exposures. Results: Applying manure and driving combines were independently associated with chronic bronchitis. Off-farm job exposures associated with chronic bronchitis were organic dusts, asbestos, gasoline, and solvents. Five pesticides were associated with chronic bronchitis after multivariate adjustment and sensitivity analyses: dichlorvos (OR = 1.63, 95% CI = 1.01, 2.61), DDT (OR = 1.67, 95% CI = 1.13, 2.47), cyanazine (OR = 1.88, 95% CI = 1.00, 3.54), paraquat (OR = 1.91, 95% CI = 1.02, 3.55), and methyl bromide (OR = 1.82, 95% CI = 1.02, 3.24). Conclusion: Pesticides as well as grain and dust exposures were associated with chronic bronchitis among nonsmoking farm women.}, number={5}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Valcin, Martin and Henneberger, Paul K. and Kullman, Greg J. and Umbach, David M. and London, Stephanie J. and Alavanja, Michael C. R. and Sandler, Dale P. and Hoppin, Jane A.}, year={2007}, month={May}, pages={574–583} } @article{koutros_mahajan_zheng_hoppin_ma_lynch_blair_alavanja_2007, title={Dichlorvos exposure and human cancer risk: results from the Agricultural Health Study}, volume={19}, ISSN={0957-5243 1573-7225}, url={http://dx.doi.org/10.1007/s10552-007-9070-0}, DOI={10.1007/s10552-007-9070-0}, abstractNote={We evaluated cancer risk from DDVP (2,2-Dichloroethenyl dimethylphosphate) exposure among pesticide applicators enrolled in the Agricultural Health Study (AHS) cohort.The AHS is a cohort of 57,311 pesticide applicators in North Carolina and Iowa, enrolled from 1993 to 1997 and followed for cancer through 2004. A comprehensive questionnaire collected information on exposure to DDVP and potential confounders. Among the 49,762 licensed pesticide applicators eligible for analysis, 4,613 reported use of DDVP. DDVP exposure was classified as intensity-weighted cumulative exposure days (IWED), calculated as [years of use x days per year x intensity level]. Poisson regression analysis was used to calculate rate ratios (RR) and 95% confidence intervals (CI) to evaluate the association of DDVP exposure among 2,943 incident cases of cancer.DDVP exposure was not associated with any cancer studied here. We observed no elevation in risk among lymphohematopoietic cancers, RR = 1.00 (95% CI 0.51, 1.96) and a small excess risk associated with exposure among those with a family history of prostate cancer (RR = 1.18 (95% CI 0.73, 1.82).We find little evidence of an association between cumulative lifetime use of DDVP and risk of any cancer at this stage of follow up of the AHS.}, number={1}, journal={Cancer Causes & Control}, publisher={Springer Science and Business Media LLC}, author={Koutros, Stella and Mahajan, Rajeev and Zheng, Tongzhang and Hoppin, Jane A. and Ma, Xiaomei and Lynch, Charles F. and Blair, Aaron and Alavanja, Michael C. R.}, year={2007}, month={Oct}, pages={59–65} } @article{bonner_coble_blair_beane freeman_hoppin_sandler_alavanja_2007, title={Malathion Exposure and the Incidence of Cancer in the Agricultural Health Study}, volume={166}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwm182}, DOI={10.1093/aje/kwm182}, abstractNote={Malathion is the most common organophosphate insecticide applied in the United States, and while some studies suggest that it may be clastogenic, its carcinogenicity has not been demonstrated in rodents. However, malathion has been associated with non-Hodgkin's lymphoma in several epidemiologic studies. The authors investigated associations between malathion exposure and cancer among 19,717 pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Information on lifetime years and days per year of use and intensity of malathion exposure was obtained with self-administered questionnaires prior to the onset of any cancer. The average follow-up time was 7.5 years (1993–2002). Rate ratios and 95% confidence intervals were calculated using Poisson regression, adjusting for potential confounders. Overall, lifetime days of malathion use (top tertile of exposure, >39 days) was not associated with all cancers combined (rate ratio = 0.97, 95% confidence interval: 0.81, 1.15). The risk of non-Hodgkin's lymphoma was not associated with malathion use, although the number of cases was small. The risk of melanoma with more than 39 lifetime exposure-days was 0.39 (95% confidence interval: 0.14, 1.03). In summary, malathion exposure was not clearly associated with cancer at any of the sites examined. Although the rate ratios for melanoma were reduced, small numbers and lack of experimental evidence suggest that the observed reductions may have arisen by chance.}, number={9}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Bonner, M. R. and Coble, J. and Blair, A. and Beane Freeman, L. E. and Hoppin, J. A. and Sandler, D. P. and Alavanja, M. C. R.}, year={2007}, month={Aug}, pages={1023–1034} } @article{lee_alavanja_hoppin_rusiecki_kamel_blair_sandler_2007, title={Mortality among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study}, volume={115}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.9662}, DOI={10.1289/ehp.9662}, abstractNote={Chlorpyrifos is one of the most widely used organophosphate insecticides in the United States. Although the toxicity of chlorpyrifos has been extensively studied in animals, the epidemiologic data are limited.To evaluate whether agricultural chlorpyrifos exposure was associated with mortality, we examined deaths among pesticide applicators in the Agricultural Health Study, a prospective study of licensed pesticide applicators in Iowa and North Carolina.A total of 55,071 pesticide applicators were included in this analysis. Detailed pesticide exposure data and other information were obtained from self-administered questionnaires completed at the time of enrollment (1993-1997). Lifetime chlorpyrifos use was divided into tertiles. Poisson regression analysis was used to evaluate the exposure-response relationships between chlorpyrifos use and causes of death after adjustment for potential confounders.A total of 1,851 deaths (588 among chlorpyrifos users) were observed during the study period, 1993-2001. The relative risk (RR) of death from all causes combined among applicators exposed to chlorpyrifos was slightly lower than that for nonexposed applicators (RR = 0.90; 95% confidence interval, 0.81-1.01). For most causes of death analyzed, there was no evidence of an exposure-response relationship. However, the relative risks for mortality from suicide and non-motor-vehicle accidents were increased 2-fold in the highest category of chlorpyrifos exposure days.Our findings of a possible association between chlorpyrifos use and external causes of death were based on small numbers. However, the findings may reflect a link between chlorpyrifos and depression or other neurobehavioral symptoms that deserves further evaluation.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Lee, Won Jin and Alavanja, Michael C.R. and Hoppin, Jane A. and Rusiecki, Jennifer A. and Kamel, Freya and Blair, Aaron and Sandler, Dale P.}, year={2007}, month={Apr}, pages={528–534} } @article{kamel_engel_gladen_hoppin_alavanja_sandler_2007, title={Neurologic symptoms in licensed pesticide applicators in the Agricultural Health Study}, volume={26}, ISSN={0960-3271 1477-0903}, url={http://dx.doi.org/10.1177/0960327107070582}, DOI={10.1177/0960327107070582}, abstractNote={Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate pesticide levels. We analysed cross-sectional data from 18 782 Caucasian, male, licensed pesticide applicators, enrolled in the Agricultural Health Study from 1993 to 1997. Applicators provided information on lifetime pesticide use, and 23 neurologic symptoms typically associated with pesticide intoxication. Increased risk of experiencing ≥10 symptoms during the year before enrollment was associated with cumulative pesticide use, personally mixing or applying pesticides, pesticide-related medical care, diagnosed pesticide poisoning, and events involving high personal pesticide exposure. Greatest risk was associated with use of organophosphate and organochlorine insecticides. Results were similar after stratification by pesticide use during the year before enrollment, or exclusion of applicators with a history of pesticide poisoning, or high-exposure events. Use of pesticide application methods likely to involve high personal exposure was associated with greater risk. Groups of symptoms reflecting several neurologic domains, including affect, cognition, autonomic and motor function, and vision, were also associated with pesticide exposure. These results suggest that neurologic symptoms are associated with cumulative exposure to moderate levels of organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.}, number={3}, journal={Human & Experimental Toxicology}, publisher={SAGE Publications}, author={Kamel, F and Engel, L S and Gladen, B C and Hoppin, J A and Alavanja, M CR and Sandler, D P}, year={2007}, month={Mar}, pages={243–250} } @article{purdue_hoppin_blair_dosemeci_alavanja_2007, title={Occupational exposure to organochlorine insecticides and cancer incidence in the Agricultural Health Study}, volume={120}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.22258}, DOI={10.1002/ijc.22258}, abstractNote={Abstract Organochlorine (OC) insecticides have been regulated as possible human carcinogens primarily on the basis of animal studies. However, the epidemiologic evidence is inconsistent. We investigated the relationship between cancer incidence and OC insecticide use among pesticide applicators enrolled in the Agricultural Health Study, a prospective cohort study of 57,311 licensed applicators in Iowa and North Carolina enrolled between 1993 and 1997. Information on ever use of 7 OC insecticides (aldrin, chlordane, DDT, dieldrin, heptachlor, lindane, toxaphene) was collected from a self‐administered questionnaire at enrollment. Lifetime exposure‐days to OC insecticides were calculated using additional data from a take‐home questionnaire completed by 25,291 participants (44% of total). We found no clear evidence of an association between use of OC insecticides and incident cancers ( N = 1,150) ascertained through December, 2002. When we focused on individual insecticides and structurally similar groups (aldrin and dieldrin; chlordane and heptachlor), significantly increased relative risks of some cancers were observed for use of some chemicals (rectal cancer and chlordane, lung cancer and dieldrin, non‐Hodgkin lymphoma (NHL) and lindane, melanoma and toxaphene, leukemia and chlordane/heptachlor). Some significant decreased relative risks were also observed (colon cancer and aldrin; overall cancer and heptachlor). In conclusion, we did not observe any clear relationship between cancer risk and the use of OC insecticides. Our chemical‐specific findings are based on small numbers and multiple comparisons, and should be interpreted with caution; however, some observed associations (lindane and NHL, chlordane/heptachlor and leukemia) are supported by previous evidence. © 2006 Wiley‐Liss, Inc.}, number={3}, journal={International Journal of Cancer}, publisher={Wiley}, author={Purdue, Mark P. and Hoppin, Jane A. and Blair, Aaron and Dosemeci, Mustafa and Alavanja, Michael C.R.}, year={2007}, month={Feb}, pages={642–649} } @article{saldana_basso_hoppin_baird_knott_blair_alavanja_sandler_2007, title={Pesticide Exposure and Self-Reported Gestational Diabetes Mellitus in the Agricultural Health Study}, volume={30}, ISSN={0149-5992 1935-5548}, url={http://dx.doi.org/10.2337/dc06-1832}, DOI={10.2337/dc06-1832}, abstractNote={To examine the association between pesticide use during pregnancy and gestational diabetes mellitus (GDM) among wives of licensed pesticide applicators.}, number={3}, journal={Diabetes Care}, publisher={American Diabetes Association}, author={Saldana, T. M. and Basso, O. and Hoppin, J. A. and Baird, D. D. and Knott, C. and Blair, A. and Alavanja, M. C.R. and Sandler, D. P.}, year={2007}, month={Feb}, pages={529–534} } @article{hoppin_valcin_henneberger_kullman_umbach_london_alavanja_sandler_2007, title={Pesticide use and chronic bronchitis among farmers in the agricultural health study}, volume={50}, ISSN={0271-3586 1097-0274}, url={http://dx.doi.org/10.1002/ajim.20523}, DOI={10.1002/ajim.20523}, abstractNote={Abstract Background Farmers have increased risk for chronic bronchitis. Few investigators have considered pesticides. Methods We evaluated pesticides as risk factors for chronic bronchitis using the Agricultural Health Study enrollment data on lifetime pesticide use and history of doctor‐diagnosed chronic bronchitis from 20,908 private pesticide applicators, primarily farmers. Results A total of 654 farmers (3%) reported chronic bronchitis diagnosed after age 19. After adjustment for correlated pesticides as well as confounders, 11 pesticides were significantly associated with chronic bronchitis. Heptachlor use had the highest odds ratio (OR = 1.50, 95% Confidence Interval (CI) = 1.19, 1.89). Increased prevalence for chronic bronchitis was also seen for individuals who had a history of a high pesticide exposure event (OR = 1.85, 95% CI = 1.51, 2.25) and for those who also applied pesticides in off‐farm jobs (OR = 1.40, 95% CI = 1.04, 1.88). Co‐morbid asthma and current farm activities did not explain these results. Conclusions These results provide preliminary evidence that pesticide use may increase chronic bronchitis prevalence. Am. J. Ind. Med. 50:969–979, 2007. © 2007 Wiley‐Liss, Inc.}, number={12}, journal={American Journal of Industrial Medicine}, publisher={Wiley}, author={Hoppin, Jane A. and Valcin, Martin and Henneberger, Paul K. and Kullman, Greg J. and Umbach, David M. and London, Stephanie J. and Alavanja, Michael C.R. and Sandler, Dale P.}, year={2007}, pages={969–979} } @article{hoppin_umbach_kullman_henneberger_london_alavanja_sandler_2007, title={Pesticides and other agricultural factors associated with self-reported farmer's lung among farm residents in the Agricultural Health Study}, volume={64}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.2006.028480}, DOI={10.1136/oem.2006.028480}, abstractNote={Farmer's lung, or hypersensitivity pneumonitis, is an important contributor to respiratory morbidity among farmers.}, number={5}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Hoppin, J. A and Umbach, D. M and Kullman, G. J and Henneberger, P. K and London, S. J and Alavanja, M. C R and Sandler, D. P}, year={2007}, month={May}, pages={334–341} } @article{lynch_rusiecki_blair_dosemeci_lubin_sandler_hoppin_lynch_alavanja_2006, title={Cancer Incidence among Pesticide Applicators Exposed to Cyanazine in theAgricultural Health Study}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.8997}, DOI={10.1289/ehp.8997}, abstractNote={BackgroundCyanazine is a common pesticide used frequently in the United States during the 1980s and 1990s. Animal and human studies have suggested that triazines may be carcinogenic, but results have been mixed. We evaluated cancer incidence in cyanazine-exposed pesticide applicators among the 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS).MethodsWe obtained detailed pesticide exposure information from a self-administered questionnaire completed at enrollment (1993–1997). Cancer incidence was followed through January 2002. Over half of cyanazine-exposed applicators had ≥ 6 years of exposure at enrollment, and approximately 85% had begun using cyanazine before the 1990s. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple cancer sites among cyanazine-exposed applicators. We calculated ptrend values, and all statistical tests were two-sided. Two exposure metrics were used: tertiles of lifetime days of exposure (LD) and intensity-weighted LD.ResultsA total of 20,824 cancer-free AHS applicators reported ever using cyanazine at enrollment. Cancer incidence comparisons between applicators with the lowest cyanazine exposure and those with the highest exposure yielded the following for the LD metric: all cancers, RR = 0.99 (95% CI, 0.80–1.24); prostate cancer, RR = 1.23 (95% CI, 0.87–1.70); all lymphohematopoietic cancers, RR = 0.92 (95% CI, 0.50–1.72); non-Hodgkin lymphoma, RR = 1.25 (95% CI, 0.47–3.35); lung cancer, RR = 0.52 (95% CI, 0.22–1.25).ConclusionsWe did not find any clear, consistent associations between cyanazine exposure and any cancer analyzed. The number of sites was small for certain cancers, limiting any conclusion with regard to ovarian, breast, and some other cancers.}, number={8}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Lynch, Shannon M. and Rusiecki, Jennifer A. and Blair, Aaron and Dosemeci, Mustafa and Lubin, Jay and Sandler, Dale and Hoppin, Jane A. and Lynch, Charles F. and Alavanja, Michael C.R.}, year={2006}, month={Aug}, pages={1248–1252} } @article{samanic_rusiecki_dosemeci_hou_hoppin_sandler_lubin_blair_alavanja_2006, title={Cancer Incidence among Pesticide Applicators Exposed to Dicamba in the Agricultural Health Study}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.9204}, DOI={10.1289/ehp.9204}, abstractNote={Dicamba is an herbicide commonly applied to crops in the United States and abroad. We evaluated cancer incidence among pesticide applicators exposed to dicamba in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in North Carolina and Iowa.}, number={10}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Samanic, Claudine and Rusiecki, Jennifer and Dosemeci, Mustafa and Hou, Lifang and Hoppin, Jane A. and Sandler, Dale P. and Lubin, Jay and Blair, Aaron and Alavanja, Michael C.R.}, year={2006}, month={Oct}, pages={1521–1526} } @article{rusiecki_hou_lee_blair_dosemeci_lubin_bonner_samanic_hoppin_sandler_et al._2006, title={Cancer incidence among pesticide applicators exposed to metolachlor in the Agricultural Health Study}, volume={118}, ISSN={0020-7136 1097-0215}, url={http://dx.doi.org/10.1002/ijc.21758}, DOI={10.1002/ijc.21758}, abstractNote={Abstract Metolachlor is one of the most widely used herbicides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to metolachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 50,193 pesticide applicators were included. Detailed information on pesticide exposure and lifestyle factors was obtained from self‐administered enrollment questionnaires completed between 1993 and 1997; average length of follow‐up was 7.33 years. Two metolachlor exposure metrics were used : ( i ) lifetime days personally mixed or applied metolachlor and ( ii ) intensity‐weighted lifetime days (lifetime days × an intensity level). Poisson regression analysis was used to estimate relative risks (RR) and 95% confidence intervals (95%CI) for cancer subtypes by tertiles of metolachlor exposure. No clear risk for any cancer subtype was found for exposure to metolachlor. A significantly decreased RR was found for prostate cancer in the highest category of lifetime days exposure (RR = 0.59; 95%CI, 0.39–0.89) and in the second highest category of intensity‐weighted lifetime days exposure (RR = 0.66; 95%CI, 0.45–0.97); however, the test for trend was not significant for either exposure metric. A nonsignificantly increased risk was found for lung cancer with lifetime days exposure in the highest category (RR = 2.37; 95%CI, 0.97–5.82, p ‐trend = 0.03) but not with intensity‐weighted lifetime days. Given the widespread use of metolachlor and the frequent detection of metolachlor in both surface and ground water, future analyses of the AHS will allow further examination of long‐term health effects, including lung cancer and the less common cancers. © 2006 Wiley‐Liss, Inc.}, number={12}, journal={International Journal of Cancer}, publisher={Wiley}, author={Rusiecki, Jennifer A. and Hou, Lifang and Lee, Won Jin and Blair, Aaron and Dosemeci, Mustafa and Lubin, Jay H. and Bonner, Matthew and Samanic, Claudine and Hoppin, Jane A. and Sandler, Dale P. and et al.}, year={2006}, pages={3118–3123} } @article{flower_hoppin_shore_lynch_blair_knott_alavanja_sandler_2006, title={Causes of Mortality and Risk Factors for Injury Mortality Among Children in the Agricultural Health Study}, volume={11}, ISSN={1059-924X 1545-0813}, url={http://dx.doi.org/10.1300/J096v11n03_06}, DOI={10.1300/J096v11n03_06}, abstractNote={Farm children face unique health risks due to sharing their residential environment with hazardous machinery and materials. Causes of mortality among farm children have not been comprehensively described.In the Agricultural Health Study (AHS) cohort, we examined causes of mortality among 21,360 children in Iowa and North Carolina between 1975 and 1998.We matched identifying information for children provided by mothers on self-administered questionnaires to state death registries (1975-1998). Data on farm and family characteristics were provided by parents via enrollment questionnaires (1993-1997). Standardized mortality ratios (SMRs) were calculated, using state mortality data to generate expected deaths. We used logistic regression to examine parent, child and farm characteristics associated with injury mortality.There were 162 deaths in Iowa (SMR = 0.69; 95% confidence interval (CI) = 0.60, 0.81) and 26 deaths in North Carolina (SMR = 0.42; 95% CI = 0.28, 0.61) in children aged 0-19 years. This deficit was largely due to deaths in the first year of life. Although deaths from overall unintentional injury were not increased, excess agricultural machinery mortality was observed in Iowa (SMR = 9.25; 95% CI = 5.12, 16.70). In case-control comparisons, maternal age less than 25 years at child's birth (OR = 2.17; 95% CI = 1.05, 4.49) and having more than 2 children in the family (OR = 2.79; 95% CI = 1.47, 5.30) were associated with increased child injury mortality. For children under 14 years, participation in farm work was associated with increased risk of agricultural machine-related mortality (OR = 3.92; 95% CI = 1.04, 14.78).Parent and child characteristics associated with child injury mortality could be used to target farm safety interventions.}, number={3-4}, journal={Journal of Agromedicine}, publisher={Informa UK Limited}, author={Flower, Kori B. and Hoppin, Jane A. and Shore, David L. and Lynch, Charles F. and Blair, Aaron and Knott, Charles and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2006}, month={Dec}, pages={47–59} } @article{beseler_stallones_hoppin_alavanja_blair_keefe_kamel_2006, title={Depression and Pesticide Exposures in Female Spouses of Licensed Pesticide Applicators in the Agricultural Health Study Cohort}, volume={48}, ISSN={1076-2752}, url={http://dx.doi.org/10.1097/01.jom.0000235938.70212.dd}, DOI={10.1097/01.jom.0000235938.70212.dd}, abstractNote={Objective: This nested case–control study evaluated the association between depression and pesticide exposure among women. Methods: The study population included 29,074 female spouses of private pesticide applicators enrolled in the Agricultural Health Study between 1993 and 1997. Cases were women who had physician-diagnosed depression requiring medication. Lifetime pesticide use was categorized as never mixed/applied pesticides, low exposure (up to 225 days), high exposure (>225 days), and a history of diagnosed pesticide poisoning. Results: After adjustment for state, age, race, off-farm work, alcohol, cigarette smoking, physician visits, and solvent exposure, depression was significantly associated with a history of pesticide poisoning (odds ratio [OR] = 3.26; 95% confidence interval [CI] = 1.72–6.19) but not low (OR = 1.09; CI = 0.91–1.31) or high (OR = 1.09; 95% CI = 0.91–1.31) cumulative pesticide exposure. Conclusion: Pesticide poisoning may contribute to risk of depression.}, number={10}, journal={Journal of Occupational and Environmental Medicine}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Beseler, Cheryl and Stallones, Lorann and Hoppin, Jane A. and Alavanja, Michael C. R. and Blair, Aaron and Keefe, Thomas and Kamel, Freya}, year={2006}, month={Oct}, pages={1005–1013} } @article{hoppin_adgate_eberhart_nishioka_ryan_2006, title={Environmental Exposure Assessment of Pesticides in Farmworker Homes}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.8530}, DOI={10.1289/ehp.8530}, abstractNote={Farmworkers and their families are exposed to pesticides both at work and in their homes. Environmental exposure assessment provides a means to evaluate pesticides in the environment and human contact with these chemicals through identification of sources and routes of exposure. To date, a variety of methods have been used to assess pesticide exposure among farmworker families, mostly focusing on dust and handwipe samples. While many of the methods are similar, differences in the collection, chemical analysis, and statistical analysis, can limit the comparability of results from farmworker studies. This mini-monograph discusses the strategies used to assess pesticide exposures, presents limitations in the available data for farmworkers, and suggests research needs for future studies of pesticide exposure among farmworker families.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, Jane A. and Adgate, John L. and Eberhart, Monty and Nishioka, Marcia and Ryan, P. Barry}, year={2006}, month={Jun}, pages={929–935} } @article{arcury_quandt_barr_hoppin_mccauley_grzywacz_robson_2006, title={Farmworker Exposure to Pesticides: Methodologic Issues for the Collection of Comparable Data}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.8531}, DOI={10.1289/ehp.8531}, abstractNote={The exposure of migrant and seasonal farmworkers and their families to agricultural and residential pesticides is a continuing public health concern. Pesticide exposure research has been spurred on by the development of sensitive and reliable laboratory techniques that allow the detection of minute amounts of pesticides or pesticide metabolites. The power of research on farmworker pesticide exposure has been limited because of variability in the collection of exposure data, the predictors of exposure considered, the laboratory procedures used in analyzing the exposure, and the measurement of exposure. The Farmworker Pesticide Exposure Comparable Data Conference assembled 25 scientists from diverse disciplinary and organizational backgrounds to develop methodologic consensus in four areas of farmworker pesticide exposure research: environmental exposure assessment, biomarkers, personal and occupational predictors of exposure, and health outcomes of exposure. In this introduction to this mini-monograph, first, we present the rationale for the conference and its organization. Second, we discuss some of the important challenges in conducting farmworker pesticide research, including the definition and size of the farmworker population, problems in communication and access, and the organization of agricultural work. Third, we summarize major findings from each of the conference's four foci-environmental exposure assessment, biomonitoring, predictors of exposure, and health outcomes of exposure-as well as important laboratory and statistical analysis issues that cross-cut the four foci.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Arcury, Thomas A. and Quandt, Sara A. and Barr, Dana B. and Hoppin, Jane A. and McCauley, Linda and Grzywacz, Joseph G. and Robson, Mark G.}, year={2006}, month={Jun}, pages={923–928} } @article{sallmén_baird_hoppin_blair_sandler_2006, title={Fertility and exposure to solvents among families in the Agricultural Health Study}, volume={63}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.2005.021337}, DOI={10.1136/oem.2005.021337}, abstractNote={Several studies have reported associations between solvent exposure and reduced female fertility, but the evidence is inconclusive for male fertility.To investigate the impact of solvent exposure on subfertility among families of male licensed pesticide applicators in the Agricultural Health Study cohort.The couples enrolled between 1993 and 1997. Cross-sectional questionnaire information on work tasks was used to assess exposure to solvents. The data were limited to couples (wife aged less than 40 years) with an attempt at pregnancy in the last four years (n = 2112).Twenty eight per cent of the couples were defined as subfertile (not conceiving a pregnancy after at least 12 months of unprotected intercourse, regardless of whether or not a pregnancy ultimately occurred). Adjusted subfertility odds ratios (OR) for exposure to solvents were calculated with logistic regression. Female (OR 1.42, 95% CI 1.15 to 1.75) and male exposure to solvents (OR 1.21 (95% CI 0.93 to 1.57) for monthly exposure and 1.40 (95% CI 0.97 to 2.03) for daily or weekly exposure) were associated with subfertility. In farming, spouses may share or exchange jobs. To account for potential dual exposure, variables for parental exposure (either parent exposed or both parents exposed) were also defined. Both were strongly associated with subfertility (OR 1.62 (95% CI 1.20 to 2.17) and OR 2.10 (95% CI 1.22 to 3.60), respectively).Solvents may impair fertility of either gender, though the evidence for female effects is stronger than for male effects.}, number={7}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Sallmén, M and Baird, D.D. and Hoppin, J.A. and Blair, A. and Sandler, D.P.}, year={2006}, month={May}, pages={469–475} } @article{mahajan_blair_lynch_schroeder_hoppin_sandler_alavanja_2006, title={Fonofos Exposure and Cancer Incidence in the Agricultural Health Study}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.9301}, DOI={10.1289/ehp.9301}, abstractNote={The Agricultural Health Study (AHS) is a prospective cohort study of licensed pesticide applicators from Iowa and North Carolina enrolled 1993-1997 and followed for incident cancer through 2002. A previous investigation in this cohort linked exposure to the organophosphate fonofos with incident prostate cancer in subjects with family history of prostate cancer.This finding along with findings of associations between organophosphate pesticides and cancer more broadly led to this study of fonofos and risk of any cancers among 45,372 pesticide applicators enrolled in the AHS.Pesticide exposure and other data were collected using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RRs) and 95% confidence intervals (CIs) while controlling for potential confounders.Relative to the unexposed, leukemia risk was elevated in the highest category of lifetime (RR = 2.24; 95% CI, 0.94-5.34, Ptrend = 0.07) and intensity-weighted exposure-days (RR = 2.67; 95% CI, 1.06-6.70, Ptrend = 0.04), a measure that takes into account factors that modify pesticide exposure. Although prostate cancer risk was unrelated to fonofos use overall, among applicators with a family history of prostate cancer, we observed a significant dose-response trend for lifetime exposure-days (Ptrend = 0.02, RR highest tertile vs. unexposed = 1.77, 95% CI, 1.03-3.05; RRinteraction = 1.28, 95% CI, 1.07-1.54). Intensity-weighted results were similar. No associations were observed with other examined cancer sites.Further study is warranted to confirm findings with respect to leukemia and determine whether genetic susceptibility modifies prostate cancer risk from pesticide exposure.}, number={12}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Mahajan, Rajeev and Blair, Aaron and Lynch, Charles F. and Schroeder, Paul and Hoppin, Jane A. and Sandler, Dale P. and Alavanja, Michael C.R.}, year={2006}, month={Dec}, pages={1838–1842} } @article{hoppin_ulmer_calafat_barr_baker_meltzer_rønningen_2006, title={Impact of urine preservation methods and duration of storage on measured levels of environmental contaminants}, volume={16}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33646490419&partnerID=MN8TOARS}, DOI={10.1038/sj.jes.7500435}, number={1}, journal={Journal of Exposure Science and Environmental Epidemiology}, author={Hoppin, J.A. and Ulmer, R. and Calafat, A.M. and Barr, D.B. and Baker, S.V. and Meltzer, H.M. and Rønningen, K.S.}, year={2006}, pages={39–48} } @article{selgrade_lemanske_gilmour_neas_ward_henneberger_weissman_hoppin_dietert_sly_et al._2006, title={Induction of Asthma and the Environment: What We Know and Need to Know}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.8376}, DOI={10.1289/ehp.8376}, abstractNote={The prevalence of asthma has increased dramatically over the last 25 years in the United States and in other nations as a result of ill-defined changes in living conditions in modern society. On 18 and 19 October 2004 the U.S. Environmental Protection Agency and the National Institute of Environmental Health Sciences sponsored the workshop "Environmental Influences on the Induction and Incidence of Asthma" to review current scientific evidence with respect to factors that may contribute to the induction of asthma. Participants addressed two broad questions: a) What does the science suggest that regulatory and public health agencies could do now to reduce the incidence of asthma? and b) What research is needed to improve our understanding of the factors that contribute to the induction of asthma and our ability to manage this problem? In this article (one of four articles resulting from the workshop), we briefly characterize asthma and its public health and economic impacts, and intervention strategies that have been successfully used to prevent induction of asthma in the workplace. We conclude with the findings of seven working groups that focus on ambient air, indoor pollutants (biologics), occupational exposures, early life stages, older adults, intrinsic susceptibility, and lifestyle. These groups found strong scientific support for public health efforts to limit in utero and postnatal exposure to cigarette smoke. However, with respect to other potential types of interventions, participants noted many scientific questions, which are summarized in this article. Research to address these questions could have a significant public health and economic impact that would be well worth the investment.}, number={4}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Selgrade, MaryJane K. and Lemanske, Robert F., Jr. and Gilmour, M. Ian and Neas, Lucas M. and Ward, Marsha D.W. and Henneberger, Paul K. and Weissman, David N. and Hoppin, Jane A. and Dietert, Rodney R. and Sly, Peter D. and et al.}, year={2006}, month={Apr}, pages={615–619} } @article{hou_lee_rusiecki_hoppin_blair_bonner_lubin_samanic_sandler_dosemeci_et al._2006, title={Pendimethalin Exposure and Cancer Incidence Among Pesticide Applicators}, volume={17}, ISSN={1044-3983}, url={http://dx.doi.org/10.1097/01.ede.0000201398.82658.50}, DOI={10.1097/01.ede.0000201398.82658.50}, abstractNote={Background: Pendimethalin, a widely used herbicide, has been classified as a group C possible human carcinogen by the U.S. Environmental Protection Agency. We evaluated the incidence of cancer in relation to reported pendimethelin use among pesticide applicators in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina. Methods: Information on pesticide use came from two questionnaires (enrollment and take-home). The present analysis includes 9089 pendimethalin-exposed and 15,285 nonpendimethalin-exposed pesticide applicators with complete information on pendimethalin use and covariates from a take-home questionnaire. We conducted Poisson regression analyses to evaluate the association of pendimethalin exposure with cancer incidence (mean follow-up = 7.5 years) using two exposure metrics: tertiles of lifetime days of exposure and tertiles of intensity-weighted lifetime days of exposure. Results: Overall cancer incidence did not increase with increasing lifetime pendimethalin use, and there was no clear evidence of an association between pendimethalin use and risks for specific cancers. The risk for rectal cancer rose with increasing lifetime pendimethalin exposure when using nonexposed as the reference (rate ratio = 4.3; 95% confidence interval = 1.5–12.7 for the highest exposed subjects; P for trend = 0.007), but the association was attenuated when using the low exposed as the referent group (P for trend = 0.08). Similar patterns for rectal cancer were observed when using intensity-weighted exposure-days. The number of rectal cancer cases among the pendimethalin-exposed was small (n = 19). There was some evidence for an elevated risk for lung cancer, but the excess occurred only in the highest exposure category for lifetime pendimethalin exposure. The trends for lung cancer risk were inconsistent for different exposure metrics. Conclusions: We did not find a clear association of lifetime pendimethalin exposure either with overall cancer incidence or with specific cancer sites.}, number={3}, journal={Epidemiology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Hou, Lifang and Lee, Won Jin and Rusiecki, Jennifer and Hoppin, Jane A. and Blair, Aaron and Bonner, Matthew R. and Lubin, Jay H. and Samanic, Claudine and Sandler, Dale P. and Dosemeci, Mustafa and et al.}, year={2006}, month={May}, pages={302–307} } @article{kamel_tanner_umbach_hoppin_alavanja_blair_comyns_goldman_korell_langston_et al._2006, title={Pesticide Exposure and Self-reported Parkinson's Disease in the Agricultural Health Study}, volume={165}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/kwk024}, DOI={10.1093/aje/kwk024}, abstractNote={Previous studies based on limited exposure assessment have suggested that Parkinson's disease (PD) is associated with pesticide exposure. The authors used data obtained from licensed private pesticide applicators and spouses participating in the Agricultural Health Study to evaluate the relation of self-reported PD to pesticide exposure. Cohort members, who were enrolled in 1993-1997, provided detailed information on lifetime pesticide use. At follow-up in 1999-2003, 68% of the cohort was interviewed. Cases were defined as participants who reported physician-diagnosed PD at enrollment (prevalent cases, n = 83) or follow-up (incident cases, n = 78). Cases were compared with cohort members who did not report PD (n = 79,557 at enrollment and n = 55,931 at follow-up). Incident PD was associated with cumulative days of pesticide use at enrollment (for highest quartile vs. lowest, odds ratio (OR) = 2.3, 95% confidence interval: 1.2, 4.5; p-trend = 0.009), with personally applying pesticides more than half the time (OR = 1.9, 95% confidence interval: 0.7, 4.7), and with some specific pesticides (ORs > or = 1.4). Prevalent PD was not associated with overall pesticide use. This study suggests that exposure to certain pesticides may increase PD risk. Findings for specific chemicals may provide fruitful leads for further investigation.}, number={4}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Kamel, F and Tanner, C. and Umbach, D. and Hoppin, J. and Alavanja, M. and Blair, A and Comyns, K and Goldman, S. and Korell, M and Langston, J. and et al.}, year={2006}, month={Nov}, pages={364–374} } @article{farr_cai_savitz_sandler_hoppin_cooper_2006, title={Pesticide Exposure and Timing of Menopause}, volume={163}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwj099}, DOI={10.1093/aje/kwj099}, abstractNote={Age at menopause has implications for fertility and risk of hormonally related chronic diseases. Some pesticides disrupt reproductive hormones or are toxic to the ovary, but little is known about the association between pesticide exposure and timing of menopause. Cox proportional hazards modeling was used to examine the association between use of pesticides and age at menopause among 8,038 women living and working on farms in Iowa and North Carolina. Premenopausal women aged 35-55 years were followed from enrollment (1993-1997) to the date of their last menstrual period, or their follow-up interview (1999-2003) if still premenopausal. Women who experienced surgical menopause were censored at the date of surgery. Approximately 62% of the women reported ever mixing or applying pesticides; women who had never used pesticides were the comparison group for all analyses. After control for age, smoking status, and past use of oral contraceptives, the median time to menopause increased by approximately 3 months for women who used pesticides (hazard ratio = 0.87, 95% confidence interval: 0.78, 0.97) and by approximately 5 months for women who used hormonally active pesticides (hazard ratio = 0.77, 95% confidence interval: 0.65, 0.92). Pesticide use may be associated with a later age at menopause.}, number={8}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Farr, Sherry L. and Cai, Jianwen and Savitz, David A. and Sandler, Dale P. and Hoppin, Jane A. and Cooper, Glinda S.}, year={2006}, month={Feb}, pages={731–742} } @article{hoppin_umbach_london_lynch_alavanja_sandler_2006, title={Pesticides and Adult Respiratory Outcomes in the Agricultural Health Study}, volume={1076}, ISSN={0077-8923}, url={http://dx.doi.org/10.1196/annals.1371.044}, DOI={10.1196/annals.1371.044}, abstractNote={Abstract: In the 1700s, Bernardino Ramazzini was among the first to describe respiratory disease among agricultural workers. Since then, farmers continue to have higher rates of respiratory illnesses, even as changes occur in occupational and environmental exposures on farms. While grain and animal exposures have been well studied for their role in agricultural lung diseases, pesticide exposures have not. Using the Agricultural Health Study, a prospective cohort study of ∼89,000 licensed pesticide applicators and their spouses in Iowa and North Carolina, we are currently assessing the association of pesticides with respiratory outcomes, including wheeze, adult asthma, farmer's lung, and chronic bronchitis. At enrollment (1993–1997), 19% of farmers and 22% of commercial pesticide applicators reported wheeze in the previous year. Using logistic regression models adjusted for age, state, smoking status, and body mass index, we evaluated the association of 40 individual pesticides with wheeze within these two groups separately. In both groups, we observed strong evidence of an association of organophosphates with wheeze. For farmers, the organophosphates chlorpyrifos, malathion, and parathion were positively associated with wheeze; for the commercial applicators, the organophosphates chlorpyrifos, dichlorvos, and phorate were positively associated with wheeze. Chlorpyrifos was strongly associated with wheeze in a dose‐dependent manner in both groups; use of chlorpyrifos for at least 20 days per year had an odds ratio of 1.48 (95% confidence interval [CI]= 1.00–2.19) for farmers and 1.96 (95% CI = 1.05–3.66) for commercial applicators. Our wheeze results are consistent with recent animal models that support a role for organophosphates and respiratory outcomes.}, number={1}, journal={Annals of the New York Academy of Sciences}, publisher={Wiley}, author={Hoppin, J. A and Umbach, D. M and London, S. J and Lynch, C. F and Alavanja, M. C.R and Sandler, D. P}, year={2006}, month={Sep}, pages={343–354} } @article{hoppin_umbach_london_lynch_alavanja_sandler_2006, title={Pesticides associated with Wheeze among Commercial Pesticide Applicators in the Agricultural Health Study}, volume={163}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwj138}, DOI={10.1093/aje/kwj138}, abstractNote={Pesticides are potential risk factors for respiratory disease among farmers, but farmers are also exposed to other respiratory toxicants. To explore the association of pesticides with wheeze in a population without other farming exposures, the authors analyzed data from 2,255 Iowa commercial pesticide applicators enrolled in the Agricultural Health Study. Controlling for age, smoking status, asthma and atopy history, and body mass index, the authors calculated odds ratios for the relationship between wheeze and 36 individual pesticides participants had used during the year before enrollment (1993–1997). Eight of 16 herbicides were associated with wheeze in single-agent models; however, the risk was almost exclusively associated with the herbicide chlorimuron-ethyl (odds ratio (OR) = 1.62, 95% confidence interval (CI): 1.25, 2.10). Inclusion of chlorimuron-ethyl in models for the other herbicides virtually eliminated the associations. The odds ratios for four organophosphate insecticides (terbufos, fonofos, chlorpyrifos, and phorate) were elevated when these chemicals were modeled individually and remained elevated, though attenuated somewhat, when chlorimuron-ethyl was included. The association for dichlorvos, another organophosphate insecticide, was not attenuated by chlorimuron-ethyl (OR = 2.48, 95% CI: 1.08, 5.66). Dose-response trends were observed for chlorimuron-ethyl, chlorpyrifos, and phorate; the strongest odds ratio was for applying chlorpyrifos on more than 40 days per year (OR = 2.40, 95% CI: 1.24, 4.65). These results add to the emerging literature linking organophosphate insecticides and respiratory health and suggest a role for chlorimuron-ethyl.}, number={12}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Hoppin, Jane A. and Umbach, David M. and London, Stephanie J. and Lynch, Charles F. and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2006}, month={Apr}, pages={1129–1137} } @article{mahajan_bonner_hoppin_alavanja_2006, title={Phorate Exposure and Incidence of Cancer in the Agricultural Health Study}, volume={114}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.8911}, DOI={10.1289/ehp.8911}, abstractNote={We recently reported a link between use of the organophosphate pesticide phorate and risk of prostate cancer among applicators with a family history of prostate cancer in the Agricultural Health Study (AHS).This finding, together with findings of associations between other organophosphate pesticides and cancer more broadly, prompted us to examine phorate exposure and overall cancer incidence in the AHS. Adding 3 years of follow-up and using more detailed exposure information allowed us to see whether the prostate cancer finding held.The AHS is a prospective study of licensed restricted-use pesticide applicators from North Carolina and Iowa. To our knowledge, this is the largest examination of workers occupationally exposed to phorate. Pesticide exposure and other information was collected using two self-administered questionnaires completed from 1993 to 1997. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CI), adjusting for potential confounders.Phorate use was not related to the incidence of all cancers combined or to any individual cancer, although we had insufficient numbers to study non-Hodgkin lymphoma or leukemia, which have been linked to organophosphates in other studies. Although prostate cancer risk was not significantly related to phorate use overall or among those without a family history, the risk tended to increase among applicators with a family history of prostate cancer. The interaction RR was 1.53 (95% CI, 0.99-2.37).The observed statistical interaction suggests a gene-environment interaction between family history and phorate exposure in the incidence of prostate cancer, but other explanations are also possible.}, number={8}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Mahajan, Rajeev and Bonner, Matthew R. and Hoppin, Jane A. and Alavanja, Michael C.R.}, year={2006}, month={Aug}, pages={1205–1209} } @article{sallm??n_sandler_hoppin_blair_baird_2006, title={Reduced Fertility Among Overweight and Obese Men}, volume={17}, ISSN={1044-3983}, url={http://dx.doi.org/10.1097/01.ede.0000229953.76862.e5}, DOI={10.1097/01.ede.0000229953.76862.e5}, abstractNote={Background: Overweight and obese men have been reported to have lower sperm counts and hormonal changes, but data are lacking regarding effects on couple fertility. Methods: We examined the relationship between male body mass index (BMI) and infertility in couples enrolled in the Agricultural Health Study in the United States. The analysis sample was limited to couples (wife <40 years old) with an attempt at pregnancy in the last 4 years based on pregnancy and fertility data provided by wives. Infertility was defined as not conceiving a pregnancy after at least 12 months of unprotected intercourse regardless of whether or not a pregnancy ultimately occurred. Self-reported weight and height were used to calculate BMI (kg/m2). Adjusted odds ratios (aORs) for infertility associated with increases in male BMI were calculated with logistic regression. Results: Adjusting for potential confounders, a 3-unit increase in male BMI was associated with infertility (aOR = 1.12; 95% confidence interval = 1.01–1.25; n = 1329). There was a dose–response relationship, and the BMI effect was stronger when the data were limited to couples with the highest-quality infertility data. The association between BMI and infertility was similar for older and younger men, suggesting that erectile dysfunction in older men does not explain the association. Conclusions: This report of lower fertility in overweight and obese men needs replication. If the findings are robust, programs to prevent obesity may improve men's reproductive health and save medical costs for infertility treatment.}, number={5}, journal={Epidemiology}, publisher={Ovid Technologies (Wolters Kluwer Health)}, author={Sallm??n, Markku and Sandler, Dale P. and Hoppin, Jane A. and Blair, Aaron and Baird, Donna Day}, year={2006}, month={Sep}, pages={520–523} } @article{rønningen_paltiel_meltzer_nordhagen_lie_hovengen_haugen_nystad_hoppin_magnus_2006, title={The Biobank in the Norwegian Mother and Child Cohort Study | Biobanken i den norske mor og barn undersøkelsen}, volume={16}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-33644958761&partnerID=MN8TOARS}, number={1}, journal={Norsk Epidemiologi}, author={Rønningen, K.S. and Paltiel, L. and Meltzer, H.M. and Nordhagen, R. and Lie, K.K. and Hovengen, R. and Haugen, M. and Nystad, W. and Hoppin, J.A. and Magnus, P.}, year={2006}, pages={59–62} } @article{rønningen_paltiel_meltzer_nordhagen_lie_hovengen_haugen_nystad_magnus_hoppin_2006, title={The biobank of the Norwegian mother and child cohort Study: A resource for the next 100 years}, volume={21}, ISSN={0393-2990 1573-7284}, url={http://dx.doi.org/10.1007/s10654-006-9041-x}, DOI={10.1007/s10654-006-9041-x}, abstractNote={Long-term storage of biological materials is a critical component of any epidemiological study. In designing specimen repositories, efforts need to balance future needs for samples with logistical constraints necessary to process and store samples in a timely fashion.In the Norwegian Mother and Child Cohort Study (MoBa), the Biobank was charged with long-term storage of more than 380,000 biological samples from pregnant women, their partners and their children for up to 100 years.Biological specimens include whole blood, plasma, DNA and urine; samples are collected at 50 hospitals in Norway. All samples are sent via ordinary mail to the Biobank in Oslo where the samples are registered, aliquoted and DNA extracted. DNA is stored at -20 degrees C while whole blood, urine and plasma are stored at -80 degrees C.As of July 2006, over 227,000 sample sets have been collected, processed and stored at the Biobank. Currently 250-300 sets are received daily. An important part of the Biobank is the quality control program.With the unique combination of biological specimens and questionnaire data, the MoBa Study will constitute a resource for many future investigations of the separate and combined effects of genetic, environmental factors on pregnancy outcome and on human morbidity, mortality and health in general.}, number={8}, journal={European Journal of Epidemiology}, publisher={Springer Science and Business Media LLC}, author={Rønningen, Kjersti S. and Paltiel, Liv and Meltzer, Helle M. and Nordhagen, Rannveig and Lie, Kari K. and Hovengen, Ragnhild and Haugen, Margaretha and Nystad, Wenche and Magnus, Per and Hoppin, Jane A.}, year={2006}, month={Sep}, pages={619–625} } @article{de roos_blair_rusiecki_hoppin_svec_dosemeci_sandler_alavanja_2005, title={Cancer Incidence among Glyphosate-Exposed Pesticide Applicators in the Agricultural Health Study}, volume={113}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.7340}, DOI={10.1289/ehp.7340}, abstractNote={Glyphosate is a broad-spectrum herbicide that is one of the most frequently applied pesticides in the world. Although there has been little consistent evidence of genotoxicity or carcinogenicity from in vitro and animal studies, a few epidemiologic reports have indicated potential health effects of glyphosate. We evaluated associations between glyphosate exposure and cancer incidence in the Agricultural Health Study (AHS), a prospective cohort study of 57,311 licensed pesticide applicators in Iowa and North Carolina. Detailed information on pesticide use and other factors was obtained from a self-administered questionnaire completed at time of enrollment (1993-1997). Among private and commercial applicators, 75.5% reported having ever used glyphosate, of which > 97% were men. In this analysis, glyphosate exposure was defined as a) ever personally mixed or applied products containing glyphosate; b) cumulative lifetime days of use, or "cumulative exposure days" (years of use times days/year); and c) intensity-weighted cumulative exposure days (years of use times days/year times estimated intensity level). Poisson regression was used to estimate exposure-response relations between glyphosate and incidence of all cancers combined and 12 relatively common cancer subtypes. Glyphosate exposure was not associated with cancer incidence overall or with most of the cancer subtypes we studied. There was a suggested association with multiple myeloma incidence that should be followed up as more cases occur in the AHS. Given the widespread use of glyphosate, future analyses of the AHS will allow further examination of long-term health effects, including less common cancers.}, number={1}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={De Roos, Anneclaire J. and Blair, Aaron and Rusiecki, Jennifer A. and Hoppin, Jane A. and Svec, Megan and Dosemeci, Mustafa and Sandler, Dale P. and Alavanja, Michael C.}, year={2005}, month={Jan}, pages={49–54} } @article{beane freeman_bonner_blair_hoppin_sandler_lubin_dosemeci_lynch_knott_alavanja_2005, title={Cancer Incidence among Male Pesticide Applicators in the Agricultural Health Study Cohort Exposed to Diazinon}, volume={162}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwi321}, DOI={10.1093/aje/kwi321}, abstractNote={Little is known about the potential carcinogenicity associated with routine application of diazinon, a common organophosphate insecticide. The authors explored a possible association of diazinon exposure with cancer risk in the Agricultural Health Study, a prospective cohort of licensed pesticide applicators in Iowa and North Carolina enrolled in 1993–1997. A total of 23,106 male applicators provided information in a self-administered questionnaire. Among 4,961 applicators who reported using diazinon, 301 incident cancer cases were diagnosed during the follow-up period ending December 2002 compared with 968 cases among 18,145 participants who reported no use. Poisson regression was used to calculate rate ratios and 95% confidence intervals. Two quantitative exposure metrics were used: lifetime exposure days and intensity-weighted lifetime exposure days, a measure that incorporates probability of pesticide exposure with lifetime pesticide application frequency. When lifetime exposure days were used, increased risks for the highest tertile of exposure and significant tests for trend for lung cancer and leukemia were observed. No other cancer site showed an association with diazinon for the highest tertile of exposure. Because these results were based on small numbers, additional analyses are necessary as more cases accrue to clarify whether diazinon is associated with cancer risk in humans.}, number={11}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Beane Freeman, Laura E. and Bonner, Matthew R. and Blair, Aaron and Hoppin, Jane A. and Sandler, Dale P. and Lubin, Jay H. and Dosemeci, Mustafa and Lynch, Charles F. and Knott, Charles and Alavanja, Michael C. R.}, year={2005}, month={Oct}, pages={1070–1079} } @article{alavanja_sandler_lynch_knott_lubin_tarone_thomas_dosemeci_barker_hoppin_et al._2005, title={Cancer incidence in the Agricultural Health Study}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-24944553519&partnerID=MN8TOARS}, number={SUPPL. 1}, journal={Scandinavian Journal of Work, Environment and Health}, author={Alavanja, M.C.R. and Sandler, D.P. and Lynch, C.F. and Knott, C. and Lubin, J.H. and Tarone, R. and Thomas, K. and Dosemeci, M. and Barker, J. and Hoppin, J.A. and et al.}, year={2005}, pages={39–45} } @article{blair_sandler_thomas_hoppin_kamel_coble_lee_rusiecki_knott_dosemeci_et al._2005, title={Disease and injury among participants in the Agricultural Health Study}, volume={11}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-20444375789&partnerID=MN8TOARS}, number={2}, journal={Journal of Agricultural Safety and Health}, author={Blair, A. and Sandler, D. and Thomas, K. and Hoppin, J.A. and Kamel, F. and Coble, J. and Lee, W.J. and Rusiecki, J. and Knott, C. and Dosemeci, M. and et al.}, year={2005}, pages={141–150} } @article{arbes_sever_vaughn_mehta_lynch_mitchell_hoppin_spencer_sandler_zeldin_2005, title={Feasibility of Using Subject-Collected Dust Samples in Epidemiologic and Clinical Studies of Indoor Allergens}, volume={113}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.7648}, DOI={10.1289/ehp.7648}, abstractNote={Studies of indoor allergen exposures are often limited by the cost and logistics of sending technicians to homes to collect dust. In this study we evaluated the feasibility of having subjects collect their own dust samples. The objectives were to compare allergen concentrations between subject- and technician-collected samples and to examine the sample return rate. Using a dust collection device and written instructions provided to them by mail, 102 subjects collected a combined dust sample from a bed and bedroom floor. Later the same day, a technician collected a side-by-side sample. Dust samples were weighed and analyzed for the cat allergen Fel d 1 and the dust mite allergen Der p 1. Fifty additional subjects who were enrolled by telephone were mailed dust collection packages and asked to return a dust sample and questionnaire by mail. A technician did not visit their homes. Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = 0.88) and Der p 1 (r = 0.87). With allergen concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreements between methodologies ranged from 91 to 98%. Although dust weights were correlated (r = 0.48, p < 0.001), subjects collected lighter samples. Among the group of 50 subjects, 46 returned a dust sample and completed questionnaire. The median number of days to receive a sample was 15. With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiologic and clinical studies that report allergen concentration as a measure of exposure.}, number={6}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Arbes, Samuel J., Jr. and Sever, Michelle and Vaughn, Ben and Mehta, Jigna and Lynch, Jeffrey T. and Mitchell, Herman and Hoppin, Jane A. and Spencer, Harvey L. and Sandler, Dale P. and Zeldin, Darryl C.}, year={2005}, month={Jun}, pages={665–669} } @article{sever_arbes_vaughn_mehta_lynch_mitchell_hoppin_spencer_sandler_zeldin_2005, title={Feasibility of using subject-collected dust samples in epidemiological and clinical studies of indoor allergens}, volume={115}, ISSN={0091-6749}, url={http://dx.doi.org/10.1016/j.jaci.2004.12.400}, DOI={10.1016/j.jaci.2004.12.400}, abstractNote={BACKgrOUND: Epidemiological and clinical studies of indoor allergen exposures are often limited by the cost of having trained technicians make home visits. Objectives: The objectives were to compare allergen concentrations and dust weights between subject- and technician-collected samples and to examine the return rate in a group of subjects who agreed to collect a sample and return it by mail.METHODS: One hundred-two subjects volunteered to collect a combined dust sample from a bed and bedroom floor and allow a trained technician to collect a side-by-side sample later the same day. Each subject was mailed written instructions, a questionnaire and a dust collector to use with his/her own vacuum cleaner. Dust samples were weighed and analyzed for cat (Fel d 1) and dust mite (Der p 1) allergens. Fifty additional subjects were mailed collection packages and asked to return a dust sample and questionnaire by mail.RESULTS: Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = .88) and Der p 1 (r = .87). With concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreement between methods ranged from 91 to 98%. Although dust weights were correlated (r = .48, P < .001), subjects tended to collect lighter samples. Among the group of 50 subjects, 46 returned a dust sample and a completed questionnaire.CONCLUSIONS: With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiological and clinical studies that report allergen concentration as a measure of exposure. BACKgrOUND: Epidemiological and clinical studies of indoor allergen exposures are often limited by the cost of having trained technicians make home visits. Objectives: The objectives were to compare allergen concentrations and dust weights between subject- and technician-collected samples and to examine the return rate in a group of subjects who agreed to collect a sample and return it by mail. METHODS: One hundred-two subjects volunteered to collect a combined dust sample from a bed and bedroom floor and allow a trained technician to collect a side-by-side sample later the same day. Each subject was mailed written instructions, a questionnaire and a dust collector to use with his/her own vacuum cleaner. Dust samples were weighed and analyzed for cat (Fel d 1) and dust mite (Der p 1) allergens. Fifty additional subjects were mailed collection packages and asked to return a dust sample and questionnaire by mail. RESULTS: Correlations between subject- and technician-collected samples were strong for concentrations of Fel d 1 (r = .88) and Der p 1 (r = .87). With concentrations dichotomized at lower limits of detection and clinically relevant thresholds, agreement between methods ranged from 91 to 98%. Although dust weights were correlated (r = .48, P < .001), subjects tended to collect lighter samples. Among the group of 50 subjects, 46 returned a dust sample and a completed questionnaire. CONCLUSIONS: With some limitations, subject-collected dust sampling appears to be a valid and practical option for epidemiological and clinical studies that report allergen concentration as a measure of exposure.}, number={2}, journal={Journal of Allergy and Clinical Immunology}, publisher={Elsevier BV}, author={Sever, M. and Arbes, S.J., Jr. and Vaughn, B. and Mehta, J. and Lynch, J.T. and Mitchell, H. and Hoppin, J.A. and Spencer, H.L., Jr. and Sandler, D.P. and Zeldin, D.C.}, year={2005}, month={Feb}, pages={S97} } @article{farmer_lash_acquavella_de roos_svec_blair_rusiecki_dosemeci_alavanja_hoppin_et al._2005, title={Glyphosate results revisited (multiple letters) [2]}, volume={113}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-20844449731&partnerID=MN8TOARS}, number={6}, journal={Environmental Health Perspectives}, author={Farmer, D.R. and Lash, T.L. and Acquavella, J.F. and De Roos, A.J. and Svec, M.A. and Blair, A. and Rusiecki, J.A. and Dosemeci, M. and Alavanja, M.C. and Hoppin, J.A. and et al.}, year={2005} } @article{hoppin_ulmer_calafat_barr_baker_meltzer_rønningen_2005, title={Impact of urine preservation methods and duration of storage on measured levels of environmental contaminants}, volume={16}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/sj.jea.7500435}, DOI={10.1038/sj.jea.7500435}, abstractNote={Collection of urine samples in human studies involves choices regarding shipping, sample preservation, and storage that may ultimately influence future analysis. As more studies collect and archive urine samples to evaluate environmental exposures in the future, we were interested in assessing the impact of urine preservative, storage temperature, and time since collection on nonpersistent contaminants in urine samples. In spiked urine samples stored in three types of urine vacutainers (no preservative, boric acid, and chlorhexidine), we measured five groups of contaminants to assess the levels of these analytes at five time points (0, 24, 48, and 72 h, and 1 week) and at two temperatures (room temperature and 4 degrees C). The target chemicals were bisphenol A (BPA), metabolites of organophosphate (OP), carbamate, and pyrethroid insecticides, chlorinated phenols, and phthalate monoesters, and were measured using five different mass spectrometry-based methods. Three samples were analyzed at each time point, with the exception of BPA. Repeated measures analysis of variance was used to evaluate effects of storage time, temperature, and preservative. Stability was summarized with percent change in mean concentration from time 0. In general, most analytes were stable under all conditions with changes in mean concentration over time, temperature, and preservative being generally less than 20%, with the exception of the OP metabolites in the presence of boric acid. The effect of storage temperature was less important than time since collection. The precision of the laboratory measurements was high allowing us to observe small differences, which may not be important when categorizing individuals into broader exposure groups.}, number={1}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Nature}, author={Hoppin, Jane A and Ulmer, Ross and Calafat, Antonia M and Barr, Dana B and Baker, Susan V and Meltzer, Helle M and Rønningen, Kjersti S}, year={2005}, month={Jul}, pages={39–48} } @article{hoppin_2005, title={Integrating exposure measurements into epidemiologic studies in agriculture}, volume={31}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-24944501381&partnerID=MN8TOARS}, number={SUPPL. 1}, journal={Scandinavian Journal of Work, Environment and Health}, author={Hoppin, J.A.}, year={2005}, pages={115–117} } @article{blair_sandler_tarone_lubin_thomas_hoppin_samanic_coble_kamel_knott_et al._2005, title={Mortality among Participants in the Agricultural Health Study}, volume={15}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2004.08.008}, DOI={10.1016/j.annepidem.2004.08.008}, abstractNote={This analysis of the Agricultural Health Study cohort assesses the mortality experience of licensed pesticide applicators and their spouses.This report is based on 52,393 private applicators (who are mostly farmers) and 32,345 spouses of farmers in Iowa and North Carolina. At enrollment, each pesticide applicator completed a 21-page enrollment questionnaire. Mortality assessment from enrollment (1994-1997) through 2000 provided an average follow-up of about 5.3 years, 447,154 person-years, and 2055 deaths.Compared with the general population in the two states, the cohort experienced a very low mortality rate. Standardized mortality ratios (SMRs) for total mortality, cardiovascular disease, diabetes, COPD, total cancer, and cancers of the esophagus, stomach, and lung were 0.6 or lower for both farmers and spouses. These deficits varied little by farm size, type of crops or livestock on the farm, years of handling pesticides, holding a non-farm job, or length of follow up. SMRs among ever smokers were not as low as among never smokers, but were still less than 1.0 for all smoking-related causes of death. No statistically significant excesses occurred, but slightly elevated SMRs, or those near 1.0, were noted for diseases that have been associated with farming in previous studies.Several factors may contribute to the low mortality observed in this population, including the healthy worker effect typically seen in cohorts of working populations (which may decline in future years), a short follow-up interval, and a healthier lifestyle manifested through lower cigarette use and an occupation that has traditionally required high levels of physical activity.}, number={4}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Blair, Aaron and Sandler, Dale P. and Tarone, Robert and Lubin, Jay and Thomas, Kent and Hoppin, Jane A. and Samanic, Claudine and Coble, Joseph and Kamel, Freya and Knott, Charles and et al.}, year={2005}, month={Apr}, pages={279–285} } @article{kamel_engel_gladen_hoppin_alavanja_sandler_2005, title={Neurologic Symptoms in Licensed Private Pesticide Applicators in the Agricultural Health Study}, volume={113}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.7645}, DOI={10.1289/ehp.7645}, abstractNote={Exposure to high levels of many pesticides has both acute and long-term neurologic consequences, but little is known about the neurotoxicity of chronic exposure to moderate levels of pesticides. We analyzed cross-sectional data from 18,782 white male licensed private pesticide applicators enrolled in the Agricultural Health Study in 1993-1997. Applicators provided information on lifetime pesticide use and 23 neurologic symptoms typically associated with pesticide intoxication. An indicator of more symptoms (> or = 10 vs. < 10) during the year before enrollment was associated with cumulative lifetime days of insecticide use: odds ratios (95% confidence intervals) were 1.64 (1.36-1.97) for 1-50 days, 1.89 (1.58-2.25) for 51-500 days, and 2.50 (2.00-3.13) for > 500 days, compared with never users. A modest association for fumigants [> 50 days, 1.50 (1.24-1.81)] and weaker relationships for herbicides [> 500 days, 1.32 (0.99-1.75)] and fungicides [> 50 days, 1.23 (1.00-1.50)] were observed. Pesticide use within the year before enrollment was not associated with symptom count. Only associations with insecticides and fumigants persisted when all four pesticide groups were examined simultaneously. Among chemical classes of insecticides, associations were strongest for organophosphates and organochlorines. Associations with cumulative exposure persisted after excluding individuals who had a history of pesticide poisoning or had experienced an event involving high personal pesticide exposure. These results suggest that self-reported neurologic symptoms are associated with cumulative exposure to moderate levels of fumigants and organophosphate and organochlorine insecticides, regardless of recent exposure or history of poisoning.}, number={7}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Kamel, Freya and Engel, Lawrence S. and Gladen, Beth C. and Hoppin, Jane A. and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2005}, month={Jul}, pages={877–882} } @article{bonner_lee_sandler_hoppin_dosemeci_alavanja_2005, title={Occupational Exposure to Carbofuran and the Incidence of Cancer in the Agricultural Health Study}, volume={113}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.7451}, DOI={10.1289/ehp.7451}, abstractNote={Carbofuran is a carbamate insecticide registered for use on a variety of food crops including corn, alfalfa, rice, and tobacco. An estimated 5 million pounds of carbofuran is used annually in the United States, and 45% of urban African-American women have detectable levels of carbofuran in their plasma. Nitrosated carbofuran has demonstrated mutagenic properties. We examined exposure to carbofuran and several tumor sites among 49,877 licensed pesticide applicators from Iowa and North Carolina enrolled in the Agricultural Health Study. We obtained information regarding years of use, frequency of use in an average year, and when use began for 22 pesticides using self-administered questionnaires. Poisson regression was used to calculate rate ratios (RR) and 95% confidence intervals (CIs) adjusting for potential confounders. Lung cancer risk was 3-fold higher for those with > 109 days of lifetime exposure to carbofuran (RR = 3.05; 95% CI, 0.94-9.87) compared with those with < 9 lifetime exposure days, with a significant dose-response trend for both days of use per year and total years of use. However, carbofuran use was not associated with lung cancer risk when nonexposed persons were used as the referent. In addition, carbofuran exposure was not associated with any other cancer site examined. Although carbamate pesticides are suspected human carcinogens, these results should be interpreted cautiously because there was no a priori hypothesis specifically linking carbofuran to lung cancer.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Bonner, Matthew R. and Lee, Won Jin and Sandler, Dale P. and Hoppin, Jane A. and Dosemeci, Mustafa and Alavanja, Michael C. R.}, year={2005}, month={Mar}, pages={285–289} } @article{arcury_quandt_rao_doran_snively_barr_hoppin_davis_2005, title={Organophosphate pesticide exposure in farmworker family members in western North Carolina and Virginia: Case comparisons}, volume={64}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-18544367183&partnerID=MN8TOARS}, number={1}, journal={Human Organization}, author={Arcury, T.A. and Quandt, S.A. and Rao, P. and Doran, A.M. and Snively, B.M. and Barr, D.B. and Hoppin, J.A. and Davis, S.W.}, year={2005}, pages={40–51} } @article{engel_hill_hoppin_lubin_lynch_pierce_samanic_sandler_blair_alavanja_2005, title={Pesticide Use and Breast Cancer Risk among Farmers' Wives in the Agricultural Health Study}, volume={161}, ISSN={0002-9262}, url={http://dx.doi.org/10.1093/aje/kwi022}, DOI={10.1093/aje/kwi022}, abstractNote={The authors examined the association between pesticide use and breast cancer incidence among farmers' wives in a large prospective cohort study in Iowa and North Carolina. Participants were 30,454 women with no history of breast cancer prior to cohort enrollment in 1993-1997. Information on pesticide use and other information was obtained by self-administered questionnaire at enrollment from the women and their husbands. Through 2000, 309 incident breast cancer cases were identified via population-based cancer registries. Rate ratios were calculated for individual pesticides using Poisson regression, controlling for confounding factors. Breast cancer standardized incidence ratios were 0.87 (95% confidence interval: 0.74, 1.02) for women who reported ever applying pesticides and 1.05 (95% confidence interval: 0.89, 1.24) for women who reported never applying pesticides. There was some evidence of increased risk associated with use of 2,4,5-trichloro-phenoxypropionic acid (2,4,5-TP) and possibly use of dieldrin, captan, and 2,4,5-trichlorophenoxyacetic acid (2,4,5-TP), but small numbers of cases among those who had personally used the pesticides precluded firm conclusions. The authors found no clear association of breast cancer risk with farm size or washing of clothes worn during pesticide application, but risk was modestly elevated among women whose homes were closest to areas of pesticide application. Further follow-up of this cohort should help clarify the relation between pesticide exposure and breast cancer risk.}, number={2}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Engel, L. S. and Hill, D.A. and Hoppin, J.A. and Lubin, J.H. and Lynch, C.F. and Pierce, J. and Samanic, C. and Sandler, D.P. and Blair, A. and Alavanja, M.C.}, year={2005}, month={Jan}, pages={121–135} } @article{burns_goldstein_kamel_gladen_hoppin_sandler_engel_alavanja_2005, title={Pesticides and neurologic symptoms (multiple letters) [1]}, volume={113}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-29144439284&partnerID=MN8TOARS}, number={12}, journal={Environmental Health Perspectives}, author={Burns, C. and Goldstein, D.A. and Kamel, F. and Gladen, B.C. and Hoppin, J.A. and Sandler, D.P. and Engel, L.S. and Alavanja, M.C.R.}, year={2005} } @article{poole_cullen_irons_acquavella_lee_hoppin_blair_lubin_dosemeci_sandler_et al._2005, title={Re: "Cancer incidence among pesticide applicators exposed to alachlor in the agricultural health study" [2] (multiple letters)}, volume={161}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-19944429315&partnerID=MN8TOARS}, DOI={10.1093/aje/kwi009}, number={1}, journal={American Journal of Epidemiology}, author={Poole, C. and Cullen, M. and Irons, R. and Acquavella, J. and Lee, W.J. and Hoppin, J.A. and Blair, A. and Lubin, J.H. and Dosemeci, M. and Sandler, D.P. and et al.}, year={2005}, pages={101–103} } @article{kirrane_hoppin_kamel_umbach_boyes_deroos_alavanja_sandler_2005, title={Retinal Degeneration and Other Eye Disorders in Wives of Farmer Pesticide Applicators Enrolled in the Agricultural Health Study}, volume={161}, ISSN={1476-6256 0002-9262}, url={http://dx.doi.org/10.1093/aje/kwi140}, DOI={10.1093/aje/kwi140}, abstractNote={Retinal degeneration is the leading cause of visual impairment in older adults. An association between retinal degeneration and fungicide use was observed previously among farmer pesticide applicators in the Agricultural Health Study, a large study of farm families from Iowa and North Carolina. The objective of this investigation was to determine whether wives of these farmer pesticide applicators were at increased risk of retinal degeneration. Self-reported cross-sectional data obtained via questionnaire between 1993 and 1997 from 31,173 wives were used. Associations of specific pesticides and groups of pesticides based on function (fungicides, herbicides, insecticides, and fumigants) or chemical structure (organophosphates, organochlorines, and carbamates) with eye disorders were evaluated using logistic and hierarchical logistic regression analyses. Self-reported retinal degeneration was associated with the wife's fungicide use (odds ratio = 1.9, 95% confidence interval: 1.2, 3.1) after adjustment for age and state of residence. Specific fungicides that appeared to drive this association were maneb or mancozeb and ziram. No associations between pesticide use and other eye disorders were found. Although these findings for retinal degeneration are based solely on self-reported disease, they are consistent with those reported for farmer pesticide applicators. These findings suggest that exposure to some fungicides and other pesticides may increase the risk of retinal degeneration and warrant further investigation.}, number={11}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Kirrane, Ellen F. and Hoppin, Jane A. and Kamel, Freya and Umbach, David M. and Boyes, William K. and DeRoos, Anneclaire J. and Alavanja, Michael and Sandler, Dale P.}, year={2005}, month={Jun}, pages={1020–1029} } @article{quandt_arcury_rao_snively_camann_doran_yau_hoppin_jackson_2004, title={Agricultural and residential pesticides in wipe samples from farmworker family residences in North Carolina and Virginia.}, volume={112}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.6554}, DOI={10.1289/ehp.6554}, abstractNote={Children of farmworkers can be exposed to pesticides through multiple pathways, including agricultural take-home and drift as well as residential applications. Because farmworker families often live in poor-quality housing, the exposure from residential pesticide use may be substantial. We measured eight locally reported agricultural pesticides and 13 pesticides commonly found in U.S. houses in residences of 41 farmworker families with at least one child < 7 years of age in western North Carolina and Virginia. Wipe samples were taken from floor surfaces, toys, and children's hands. We also collected interview data on possible predictors of pesticide presence, including characteristics of the household residents, cleaning practices, and characteristics of the home. All families were Spanish-speaking, primarily from Mexico. Results indicate that six agricultural and 11 residential pesticides were found in the homes, with agricultural, residential, or both present in 95% of homes sampled. In general, residential pesticides were more commonly found. Presence of both types of pesticides on the floor was positively associated with detection on toys or hands. Agricultural pesticide detection was associated with housing adjacent to agricultural fields. Residential pesticide detection was associated with houses judged difficult to clean. Although the likelihood of agricultural pesticide exposure has been considered high for farmworker families, these results indicate that residential pesticide use and exposure in this population merit further study.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Quandt, Sara A and Arcury, Thomas A and Rao, Pamela and Snively, Beverly M and Camann, David E and Doran, Alicia M and Yau, Alice Y and Hoppin, Jane A and Jackson, David S}, year={2004}, month={Mar}, pages={382–387} } @article{kamel_hoppin_2004, title={Association of Pesticide Exposure with Neurologic Dysfunction and Disease}, volume={112}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.7135}, DOI={10.1289/ehp.7135}, abstractNote={Poisoning by acute high-level exposure to certain pesticides has well-known neurotoxic effects, but whether chronic exposure to moderate levels of pesticides is also neurotoxic is more controversial. Most studies of moderate pesticide exposure have found increased prevalence of neurologic symptoms and changes in neurobehavioral performance, reflecting cognitive and psychomotor dysfunction. There is less evidence that moderate exposure is related to deficits in sensory or motor function or peripheral nerve conduction, but fewer studies have considered these outcomes. It is possible that the most sensitive manifestation of pesticide neurotoxicity is a general malaise lacking in specificity and related to mild cognitive dysfunction, similar to that described for Gulf War syndrome. Most studies have focused on organophosphate insecticides, but some found neurotoxic effects from other pesticides, including fungicides, fumigants, and organochlorine and carbamate insecticides. Pesticide exposure may also be associated with increased risk of Parkinson disease; several classes of pesticides, including insecticides, herbicides, and fungicides, have been implicated. Studies of other neurodegenerative diseases are limited and inconclusive. Future studies will need to improve assessment of pesticide exposure in individuals and consider the role of genetic susceptibility. More studies of pesticides other than organophosphates are needed. Major unresolved issues include the relative importance of acute and chronic exposure, the effect of moderate exposure in the absence of poisoning, and the relationship of pesticide-related neurotoxicity to neurodegenerative disease.}, number={9}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Kamel, Freya and Hoppin, Jane A.}, year={2004}, month={Jun}, pages={950–958} } @article{rusiecki_de roos_lee_dosemeci_lubin_hoppin_blair_alavanja_2004, title={Cancer Incidence Among Pesticide Applicators Exposed to Atrazine in the Agricultural Health Study}, volume={96}, ISSN={0027-8874 1460-2105}, url={http://dx.doi.org/10.1093/jnci/djh264}, DOI={10.1093/jnci/djh264}, abstractNote={Background: Atrazine is the most heavily applied agricultural pesticide for crop production in the United States. Both animal and human studies have suggested that atrazine is possibly carcinogenic, but results have been mixed. We evaluated cancer incidence in atrazine-exposed pesticide applicators among 53 943 participants in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Methods: We obtained detailed pesticide exposure information using a self-administered questionnaire completed at the time of enrollment (1993–1997). Cancer incidence was followed through December 31, 2001. We used adjusted Poisson regression to calculate rate ratios (RRs) and 95% confidence intervals (CIs) of multiple types of cancer among atrazine exposed applicators. Ptrend values were calculated using atrazine exposure as a continuous variable, and all statistical tests were two-sided. Two exposure metrics were used: quartiles of lifetime days of exposure and quartiles of intensity-weighted lifetime days of exposure. Results: 36 513 (68%) applicators reported ever using atrazine; exposure was not associated with overall cancer incidence. Comparisons of cancer incidence in applicators with the highest atrazine exposure and those with the lowest exposure, assessed by lifetime days (RR LD ) and intensity-weighted lifetime days (RR IWLD ) of exposure yielded the following results: prostate cancer, RR LD = 0.88, 95% CI = 0.63 to 1.23, Ptrend = .26, and RR IWLD = 0.89, 95% CI = 0.63 to 1.25, Ptrend = .35; lung cancer, RR LD = 1.91, 95% CI = 0.93 to 3.94, Ptrend = .08, and RR IWLD = 1.37, 95% CI = 0.65 to 2.86, Ptrend = .19; bladder cancer, RR LD = 3.06, 95% CI = 0.86 to 10.81, Ptrend =.18, and RR IWLD = 0.85, 95% CI = 0.24 to 2.94, Ptrend = .71; non-Hodgkin lymphoma, RR LD = 1.61, 95% CI = 0.62 to 4.16, Ptrend = .35, and RR IWLD = 1.75, 95% CI = 0.73 to 4.20, Ptrend = .14; and multiple myeloma, RR LD = 1.60, 95% CI = 0.37 to 7.01, Ptrend = .41, and RR IWLD = 2.17, 95% CI = 0.45 to 10.32, Ptrend = .21. Conclusions: Our analyses did not find any clear associations between atrazine exposure and any cancer analyzed. However, further studies are warranted for tumor types in which there was a suggestion of trend (lung, bladder, non-Hodgkin lymphoma, and multiple myeloma).}, number={18}, journal={JNCI Journal of the National Cancer Institute}, publisher={Oxford University Press (OUP)}, author={Rusiecki, J. A. and De Roos, A. and Lee, W. J. and Dosemeci, M. and Lubin, J. H. and Hoppin, J. A. and Blair, A. and Alavanja, M. C. R.}, year={2004}, month={Sep}, pages={1375–1382} } @article{lee_blair_hoppin_lubin_rusiecki_sandler_dosemeci_alavanja_2004, title={Cancer Incidence Among Pesticide Applicators Exposed to Chlorpyrifos in the Agricultural Health Study}, volume={96}, ISSN={0027-8874 1460-2105}, url={http://dx.doi.org/10.1093/jnci/djh324}, DOI={10.1093/jnci/djh324}, abstractNote={Chlorpyrifos is one of the most widely used insecticides in the United States. We evaluated the incidence of cancer among pesticide applicators exposed to chlorpyrifos in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina.A total of 54,383 pesticide applicators were included in this analysis. Detailed information on pesticide exposure and lifestyle factors was obtained from self-administered questionnaires completed at the time of enrollment (December 1993-December 1997). Poisson regression analysis was used to evaluate the association between chlorpyrifos exposure and cancer incidence after adjustment for potential confounders. All statistical tests were two-sided.A total of 2070 incident malignant neoplasms were diagnosed through 2001. The rate ratio for all cancers combined among chlorpyrifos-exposed applicators compared with nonexposed applicators was 0.97 (95% confidence interval = 0.87 to 1.08). For most cancers analyzed, there was no evidence of an exposure-response relationship. However, the incidence of lung cancer was statistically significantly associated with both chlorpyrifos lifetime exposure-days (P(trend) = .002) and chlorpyrifos intensity-weighted exposure-days (P(trend) = .036). After adjustment for other pesticide exposures and demographic factors, individuals in the highest quartile of chlorpyrifos lifetime exposure-days (>56 days) had a relative risk of lung cancer 2.18 (95% confidence interval = 1.31 to 3.64) times that of those with no chlorpyrifos exposure.Our findings suggest an association between chlorpyrifos use and incidence of lung cancer that deserves further evaluation.}, number={23}, journal={JNCI Journal of the National Cancer Institute}, publisher={Oxford University Press (OUP)}, author={Lee, W. J. and Blair, A. and Hoppin, J. A. and Lubin, J. H. and Rusiecki, J. A. and Sandler, D. P. and Dosemeci, M. and Alavanja, M. C. R.}, year={2004}, month={Nov}, pages={1781–1789} } @article{lee_hoppin_blair_lubin_dosemeci_sandler_alavanja_2004, title={Cancer Incidence among Pesticide Applicators Exposed to Alachlor in the Agricultural Health Study}, volume={159}, ISSN={0002-9262}, url={http://dx.doi.org/10.1093/aje/kwh040}, DOI={10.1093/aje/kwh040}, abstractNote={The authors evaluated the incidence of cancer among pesticide applicators with exposure to alachlor in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. A total of 49,980 pesticide applicators are included in this analysis; 26,510 applicators (53%) reported use of alachlor on the enrollment questionnaire. Detailed pesticide exposure and other information were obtained from a self-administered questionnaire completed at the time of enrollment (1993-1997). Poisson regression analysis was used to evaluate the exposure-response relations between alachlor and cancer incidence controlled for the effects of potential confounding factors. A total of 1,466 incident malignant neoplasms were diagnosed during the study period, 1993-2000. Among alachlor-exposed applicators, the authors found a significant increasing trend for incidence of all lymphohematopoietic cancers associated with lifetime exposure-days (p for trend = 0.02) and intensity-weighted exposure-days (p for trend = 0.03) to alachlor. The risks of leukemia (rate ratio = 2.83, 95% confidence interval: 0.74, 10.9) and multiple myeloma (rate ratio = 5.66, 95% confidence interval: 0.70, 45.7) were increased among applicators in the highest alachlor exposure category. Our findings suggest a possible association between alachlor application and incidence of lymphohematopoietic cancers among applicators in the Agricultural Health Study.}, number={4}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Lee, W. J. and Hoppin, J.A. and Blair, A. and Lubin, J.H. and Dosemeci, M. and Sandler, D.P. and Alavanja, M.C.R.}, year={2004}, month={Feb}, pages={373–380} } @article{flower_hoppin_lynch_blair_knott_shore_sandler_2004, title={Cancer risk and parental pesticide application in children of Agricultural Health Study participants.}, volume={112}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.6586}, DOI={10.1289/ehp.6586}, abstractNote={Parental exposure to pesticides may contribute to childhood cancer risk. Through the Agricultural Health Study, a prospective study of pesticide applicators in Iowa and North Carolina, we examined childhood cancer risk and associations with parental pesticide application. Identifying information for 17,357 children of Iowa pesticide applicators was provided by parents via questionnaires (1993-1997) and matched against the Iowa Cancer Registry. Fifty incident childhood cancers were identified (1975-1998). Risk of all childhood cancers combined was increased [standardized incidence ratio (SIR) = 1.36; 95% confidence interval (CI), 1.03-1.79]. Risk of all lymphomas combined was also increased (SIR = 2.18; 95% CI, 1.13-4.19), as was risk of Hodgkin's lymphoma (SIR = 2.56; 95% CI, 1.06-6.14). We used logistic regression to explore associations between self-reported parental pesticide application practices and childhood cancer risk. No association was detected between frequency of parental pesticide application and childhood cancer risk. An increased risk of cancer was detected among children whose fathers did not use chemically resistant gloves [odds ratio (OR) = 1.98; 95% CI, 1.05-3.76] compared with children whose fathers used gloves. Of 16 specific pesticides used by fathers prenatally, ORs were increased for aldrin (OR = 2.66), dichlorvos (OR = 2.06), and ethyl dipropylthiocarbamate (OR = 1.91). However, these results were based on small numbers and not supported by prior biologic evidence. Identification of excess lymphoma risk suggests that farm exposures including pesticides may play a role in the etiology of childhood lymphoma.}, number={5}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Flower, Kori B and Hoppin, Jane A and Lynch, Charles F and Blair, Aaron and Knott, Charles and Shore, David L and Sandler, Dale P}, year={2004}, month={Apr}, pages={631–635} } @article{flower_hoppin_lynch_blair_knott_shore_sandler_2004, title={Cancer risk and parental pesticide application in children's of agricultural health study participants}, volume={112}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-16544378273&partnerID=MN8TOARS}, number={5}, journal={Environmental Health Perspectives}, author={Flower, K.B. and Hoppin, J.A. and Lynch, C.F. and Blair, A. and Knott, C. and Shore, D.L. and Sandler, D.P.}, year={2004}, pages={631–635} } @article{parks_cooper_nylander-french_hoppin_sanderson_dement_2004, title={Comparing questionnaire-based methods to assess occupational silica exposure}, volume={15}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4344581107&partnerID=MN8TOARS}, DOI={10.1097/01.ede.0000129515.54074.b2}, abstractNote={Epidemiologic assessment of occupational exposure to silica is typically limited to long-term work in the dusty trades, primarily in jobs held by men. We compared alternative questionnaire-based methods to assess silica exposure in a recent case-control study of 265 patients with systemic lupus erythematosus (mostly women) and 355 controls randomly selected from state driver's license registries and frequency-matched by age and sex.In-person interviews included a job history (all jobs held at least 12 months) and checklist of silica-related jobs and tasks (work of at least 2 weeks). Three industrial hygienists reviewed job descriptions without knowing case-control status. Potential high- or moderate-intensity exposures were confirmed or revised based on follow-up telephone interviews.In the full assessment including all work of at least 2 weeks, 9% of cases and 4% of controls were classified as medium or high silica exposure (odds ratio of disease = 2.9; 95% confidence interval = 1.3-6.4). In contrast, only 4% of cases and 9% of controls were identified by the standardized code groups index as having worked in silica-related industries or occupations for at least 12 months, providing a much lower risk estimate for disease (0.4; 0.2-0.9).Specific task-based questions must be included to assess the full potential of occupational silica exposure. These findings highlight the limitations of using standardized code groups to define exposure or to select jobs for industrial hygienist review.}, number={4}, journal={Epidemiology}, author={Parks, C.G. and Cooper, G.S. and Nylander-French, L.A. and Hoppin, J.A. and Sanderson, W.T. and Dement, J.M.}, year={2004}, pages={433–441} } @article{hoppin_umbach_london_alavanja_sandler_2004, title={Diesel Exhaust, Solvents, and Other Occupational Exposures as Risk Factors for Wheeze among Farmers}, volume={169}, ISSN={1073-449X 1535-4970}, url={http://dx.doi.org/10.1164/rccm.200309-1228OC}, DOI={10.1164/rccm.200309-1228OC}, abstractNote={Farmers engage in activities that result in exposure to diesel exhaust, solvents, welding fumes, and other respiratory irritants. Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina, we evaluated the odds of wheeze associated with nonpesticide occupational exposures. We used logistic regression models controlling for age, state, smoking, and history of asthma or atopy to evaluate odds of wheeze in the past year among the 20898 farmers who provided complete information on all covariates. Driving diesel tractors was associated with elevated odds of wheeze (odds ratio = 1.31; 95% confidence interval = 1.13, 1.52); the odds ratio for driving gasoline tractors was 1.11 (95% confidence interval = 1.02, 1.21). A duration-response relationship was observed for driving diesel tractors but not for driving gasoline tractors. Activities involving solvent exposure, including painting and use of solvents for cleaning, were associated with an increased odds of wheeze in a duration-dependent fashion. The highest odds of wheeze for farm activities were for daily painting (odds ratio = 1.82; 95% confidence interval = 0.89, 3.73), an indication of daily solvent exposure. These results add to the growing body of evidence of adverse respiratory effects of diesel exposure on the lung and suggest exposure to solvents may contribute as well.}, number={12}, journal={American Journal of Respiratory and Critical Care Medicine}, publisher={American Thoracic Society}, author={Hoppin, Jane A. and Umbach, David M. and London, Stephanie J. and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2004}, month={Jun}, pages={1308–1313} } @article{samanic_hoppin_lubin_blair_alavanja_2004, title={Factor analysis of pesticide use patterns among pesticide applicators in the Agricultural Health Study}, volume={15}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/sj.jea.7500396}, DOI={10.1038/sj.jea.7500396}, abstractNote={Exposure to certain pesticides has been linked with both acute and chronic adverse health outcomes such as neurotoxicity and risk for certain cancers. Univariate analyses of pesticide exposures may not capture the complexity of these exposures since use of various pesticides often occurs simultaneously, and because specific uses have changed over time. Using data from the Agricultural Health Study, a cohort study of 89,658 licensed pesticide applicators and their spouses in Iowa and North Carolina, we employed factor analysis to order to characterize underlying patterns of self-reported exposures to 50 different pesticides. Factor analysis is a statistical method used to explain the relationships between several correlated variables by reducing them to a smaller number of conceptually meaningful, composite variables, known as factors. Three factors emerged for farmer applicators (N=45,074): (1) Iowa agriculture and herbicide use, (2) North Carolina agriculture and use of insecticides, fumigants and fungicides, and (3) older age and use of chlorinated pesticides. The patterns observed for spouses of farmers (N=17,488) were similar to those observed for the farmers themselves, whereas five factors emerged for commercial pesticide applicators (N=4,384): (1) herbicide use, (2) older age and use of chlorinated pesticides, (3) use of fungicides and residential pest treatments, (4) use of animal insecticides, and (5) use of fumigants. Pesticide exposures did not correlate with lifestyle characteristics such as race, smoking status or education. This heterogeneity in exposure patterns may be used to guide etiologic studies of health effects of farmers and other groups exposed to pesticides.}, number={3}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Nature}, author={Samanic, Claudine and Hoppin, Jane A and Lubin, Jay H and Blair, Aaron and Alavanja, Michael C R}, year={2004}, month={Jul}, pages={225–233} } @article{alavanja_hoppin_kamel_2004, title={Health Effects of Chronic Pesticide Exposure: Cancer and Neurotoxicity}, volume={25}, ISSN={0163-7525 1545-2093}, url={http://dx.doi.org/10.1146/annurev.publhealth.25.101802.123020}, DOI={10.1146/annurev.publhealth.25.101802.123020}, abstractNote={Pesticides are widely used in agricultural and other settings, resulting in continuing human exposure. Epidemiologic studies indicate that, despite premarket animal testing, current exposures are associated with risks to human health. In this review, we describe the routes of pesticide exposures occurring today, and summarize and evaluate the epidemiologic studies of pesticide-related carcinogenicity and neurotoxicity in adults. Better understanding of the patterns of exposure, the underlying variability within the human population, and the links between the animal toxicology data and human health effects will improve the evaluation of the risks to human health posed by pesticides. Improving epidemiology studies and integrating this information with toxicology data will allow the human health risks of pesticide exposure to be more accurately judged by public health policy makers.}, number={1}, journal={Annual Review of Public Health}, publisher={Annual Reviews}, author={Alavanja, Michael C.R. and Hoppin, Jane A. and Kamel, Freya}, year={2004}, month={Apr}, pages={155–197} } @article{kirrane_hoppin_umbach_samanic_sandler_2004, title={Patterns of pesticide use and their determinants among wives of farmer pesticide applicators in the agricultural health study}, volume={46}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-4143147448&partnerID=MN8TOARS}, DOI={10.1097/01.jom.0000135521.15169.3e}, abstractNote={Pesticide exposure among farmers' wives is poorly characterized. Using questionnaire data from a cohort study of licensed pesticide applicators and their spouses, we investigated patterns of pesticide use among farmers' wives (n = 31,173). Wives reported a wide range of pesticide use: 36% never used pesticides during their lifetimes, whereas the heaviest pesticide users (10%) reported lifetime use of 3 or more agricultural pesticides plus commonly used residential pesticides. We identified 5 ordinal pesticide-use categories and studied factors associated with each category through polytomous logistic regression. Engaging in field work and household hygiene practices that could increase exposure were associated with pesticide use, and associations appeared to strengthen with increasing pesticide use category. Farm women reporting the heaviest pesticide use could exacerbate their exposure by engaging in practices that could increase pesticide contact.}, number={8}, journal={Journal of Occupational and Environmental Medicine}, author={Kirrane, E.F. and Hoppin, J.A. and Umbach, D.M. and Samanic, C. and Sandler, D.P.}, year={2004}, pages={856–865} } @article{hou_lee_rusiecki_hoppin_blair_bonner_lubin_samanic_sandler_dosemeci_et al._2004, title={Pendimethalin exposure and cancer risk among pesticide applicators: a report from the U.S.-based agricultural health study}, volume={14}, ISSN={1047-2797}, url={http://dx.doi.org/10.1016/j.annepidem.2004.07.046}, DOI={10.1016/j.annepidem.2004.07.046}, abstractNote={We evaluated the incidence of cancer in relation to pendimethalin exposure among pesticide applicators in the Agricultural Health Study, a prospective cohort study of licensed pesticide applicators in Iowa and North Carolina. Pendimethalin is a widely used herbicide, intended for the control of most annual grasses and certain broadleaf weeds in most crops. This study includes 9089 pendimethalin-exposed and 26,836 nonexposed pesticide applicators. At the time of enrollment (1993–1997), detailed information on pesticide exposure and potential confounders was obtained from a self-administered questionnaire. Poisson regression analysis was used to evaluate the effect of pendimethalin exposure, categorized into tertiles, on cancer incidence, controlling for the effects of potential confounding factors. Significant increased relative risks (RRs) for rectum cancer among subjects with the highest life-time pendimethalin exposure days were observed compared with both non-pendimethalin-exposed (RR = 3.5, 95% CI = 1.3–9.2) and low-pendimethalin-exposed (RR = 9.2, 95% CI = 1.1–81.1) applicators. We also observed an increased RR for rectum cancer when we used intensity-weighted lifetime pendimethalin exposure days as the exposure metric, using non-pendimethalin-exposed applicators as the referent group (RR = 3.5, 95% CI = 1.3–9.2, Ptrend = 0.04). Relative risk for lung cancer was also increased among subjects in the upper half of the highest tertile of life-time pendimethalin exposure days (RR = 5.2, 95% CI = 1.6–17.3, Ptrend = 0.03), compared with low-pendimethalin-exposed applicators. The association was more pronounced for adenocarcinoma of both rectum and lung. Our findings suggest a possible association between pendimethalin exposure and incidence of rectum and lung cancers among pesticide applicators in the U.S.-based Agricultural Health Study.}, number={8}, journal={Annals of Epidemiology}, publisher={Elsevier BV}, author={Hou, Lifang and Lee, Won Jin and Rusiecki, Jennifer and Hoppin, Jane A. and Blair, Aaron and Bonner, Matt and Lubin, Jay H. and Samanic, Claudine and Sandler, Dale P. and Dosemeci, Mustafa and et al.}, year={2004}, month={Sep}, pages={608} } @article{alavanja_dosemeci_samanic_lubin_lynch_knott_barker_hoppin_sandler_coble_et al._2004, title={Pesticides and Lung Cancer Risk in the Agricultural Health Study Cohort}, volume={160}, ISSN={0002-9262}, url={http://dx.doi.org/10.1093/aje/kwh290}, DOI={10.1093/aje/kwh290}, abstractNote={The authors examined the relation between 50 widely used agricultural pesticides and lung cancer incidence in the Agricultural Health Study, a prospective cohort study of 57,284 pesticide applicators and 32,333 spouses of farmer applicators with no prior history of lung cancer. Self-administered questionnaires were completed at enrollment (1993–1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 2001. A lung cancer standardized incidence ratio of 0.44 (95% confidence interval: 0.39, 0.49) was observed overall, due in large part to a low cigarette smoking prevalence. Two widely used herbicides, metolachlor and pendimethalin (for low-exposed groups to four higher exposure categories: odds ratio (OR) = 1.0, 1.6, 1.2, 5.0; ptrend = 0.0002; and OR = 1.0, 1.6, 2.1, 4.4; ptrend = 0.003, respectively), and two widely used insecticides, chlorpyrifos and diazinon (OR = 1.0, 1.1, 1.7, 1.9; ptrend = 0.03; and OR = 1.0, 1.6, 2.7, 3.7; ptrend = 0.04, respectively), showed some evidence of exposure response for lung cancer. These excesses could not be explained by previously identified lung cancer risk factors. The usage levels in this cohort are considerably higher than those typically experienced by the general population. An excess risk among spouses directly exposed to pesticides could not be evaluated at this time.}, number={9}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Alavanja, M. C. R. and Dosemeci, M. and Samanic, C. and Lubin, J. and Lynch, C.F. and Knott, C. and Barker, J. and Hoppin, J.A. and Sandler, D.P. and Coble, J. and et al.}, year={2004}, month={Nov}, pages={876–885} } @article{hoppin_ulmer_london_2004, title={Phthalate exposure and pulmonary function}, volume={112}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-11844285846&partnerID=MN8TOARS}, number={5}, journal={Environmental Health Perspectives}, author={Hoppin, J.A. and Ulmer, R. and London, S.J.}, year={2004}, pages={571–574} } @article{hoppin_ulmer_london_2004, title={Phthalate exposure and pulmonary function.}, volume={112}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.6564}, DOI={10.1289/ehp.6564}, abstractNote={Exposure to phthalates is widespread because of their use in plastics, cosmetics, and other consumer products. Phthalate exposure has been associated with adverse respiratory outcomes in children. With urinary phthalate measures, we assessed the association between phthalate exposure and four pulmonary function parameters [forced vital capacity (FVC), forced expiratory volume at 1 sec (FEV1), peak expiratory flow (PEF), and maximum mid-expiratory flow] among the 240 adult Third National Health and Nutrition Examination Survey (NHANES III) participants with urinary phthalate data. Linear regression models controlled for race, age, age squared, standing height, body mass index, cumulative smoking, and current smoking. Monobutyl phthalate (MBP) was significantly associated with decrements in three measures of pulmonary function (FVC, FEV1, PEF) in males but not in females. For a change from the 25th to the 75th percentile in MBP level among men, FEV1 decreased 112 mL (SE = 51, p = 0.03). Monoethyl phthalate (MEP) was associated with lower FVC and FEV1 values in men. Monoethylhexyl phthalate (MEHP), the metabolite of the plasticizer commonly used in medical tubing, was not adversely associated with any of the pulmonary function parameters evaluated. Our results suggest that MBP and MEP, but not MEHP, may influence pulmonary function among adult males.}, number={5}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, Jane A and Ulmer, Ross and London, Stephanie J}, year={2004}, month={Apr}, pages={571–574} } @article{quandt_doran_rao_hoppin_snively_arcury_2004, title={Reporting pesticide assessment results to farmworker families: development, implementation, and evaluation of a risk communication strategy.}, volume={112}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.6754}, DOI={10.1289/ehp.6754}, abstractNote={The collection of environmental samples presents a responsibility to return information to the affected participants. Explaining complex and often ambiguous scientific information to a lay audience is a challenge. As shown by environmental justice research, this audience frequently has limited formal education, increasing the challenge for researchers to explain the data collected, the risk indicated by the findings, and action the affected community should take. In this study we describe the development and implementation of a risk communication strategy for environmental pesticide samples collected in the homes of Latino/a migrant and seasonal farmworkers in a community-based participatory research project. The communication strategy was developed with community input and was based on face-to-face meetings with members of participating households. Using visual displays of data effectively conveyed information about individual household contamination and placed it in the context of community findings. The lack of national reference data and definitive standards for action necessitated a simplified risk message. We review the strengths and weaknesses of such an approach and suggest areas for future research in risk communication to communities affected by environmental health risks.}, number={5}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Quandt, Sara A and Doran, Alicia M and Rao, Pamela and Hoppin, Jane A and Snively, Beverly M and Arcury, Thomas A}, year={2004}, month={Apr}, pages={636–642} } @article{white_hoppin_2004, title={Seed treatment and its implication for fungicide exposure assessment}, volume={14}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/sj.jea.7500312}, DOI={10.1038/sj.jea.7500312}, abstractNote={Farmers may be exposed to fungicides through both personal application and use of treated seed. Most epidemiology studies rely on personal application to assess exposure. We explored the extent of potential exposure via use of treated seed using data from a large cohort of licensed pesticide applicators from Iowa and North Carolina. Potential secondary fungicide exposure due to treated seed was calculated by crop by multiplying the average percent of seed treated by those reporting raising that crop but not applying fungicide. This potential exposure was present for every crop with treated seed (corn, soybean, wheat, cotton, potato, and peanut), and was highest for corn (71%) and soybean farmers (19%). Potential secondary fungicide exposure was more common in Iowa than in North Carolina since most Iowa farmers plant corn and soybeans and few report applying fungicides. Owing to its widespread use on corn, potential secondary captan exposure may occur among the 90% of the individuals planting corn. The relative intensity of secondary fungicide exposure associated with planting treated seed is anticipated to be lower than actively applying fungicide. Limited data suggest that exposure during planting may be approximately 4% of actively applying fungicide; while seed transfer operations may have similar levels of exposure to personal application (80-200%). Measurement data are necessary to characterize the patterns of exposure related to the use of fungicide-treated seed and to determine whether this route of exposure is an important contributor to fungicide exposure among farmers.}, number={3}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Nature}, author={White, Katrina E and Hoppin, Jane A}, year={2004}, month={May}, pages={195–203} } @article{hoppin_2003, title={Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking}, volume={60}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.60.8.e3}, DOI={10.1136/oem.60.8.e3}, abstractNote={Exposure to animals, their feeds, and by-products contribute to respiratory symptoms among farmers.To investigate the role of animal exposures and wheeze, and to assess whether their impact differs among susceptible subgroups, including atopics, asthmatics, and smokers.Using the Agricultural Health Study, a cohort of pesticide applicators in Iowa and North Carolina enrolled in 1994-97, wheeze associated with animal production was evaluated and interactions among susceptible subgroups assessed. Logistic regression models were used to examine risk factors for wheeze in the past year among 20 468 farmers.Individuals raising animals requiring direct contact had the highest odds ratios (OR) for wheeze (OR(dairy) = 1.26; OR(eggs) = 1.70). A significant dose response was observed for both the number of poultry and the number of livestock on the farm. Farmers who performed veterinary procedures on a daily basis had an OR of 1.51. The odds of wheeze associated with poultry production was greater among atopic than non-atopic individuals. Milking cows daily increased the odds of wheeze in all individuals, with the largest association observed among atopic asthmatic individuals. The impact of dairy, poultry, and egg production varied among smoking groups. Past smokers had the highest odds ratios, followed by never smokers, and then current smokers. The OR(eggs) was 2.88 among past smokers but only 1.46 for never smokers. The OR(eggs) for current smokers of 0.80 might reflect self selection of exposure among smokers.Results are consistent with animal production and respiratory symptoms, and suggest that subgroups may respond differently to exposure.}, number={8}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Hoppin, J A}, year={2003}, month={Aug}, pages={3e–3} } @article{hoppin_umbach_london_alavanja_sandler_2003, title={Animal production and wheeze in the Agricultural Health Study: interactions with atopy, asthma, and smoking.}, volume={60}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0141454811&partnerID=MN8TOARS}, number={8}, journal={Occupational and environmental medicine}, author={Hoppin, J.A. and Umbach, D.M. and London, S.J. and Alavanja, M.C. and Sandler, D.P.}, year={2003} } @article{hoppin_2003, title={Male reproductive effects of phthalates: An emerging picture}, volume={14}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0038672685&partnerID=MN8TOARS}, DOI={10.1097/00001648-200305000-00002}, abstractNote={Like so many other byproducts of human enterprise, phthalates, without much attention paid to their possible health effects, have become widely distributed among people. In 2000, the Centers for Disease Control and Prevention (CDC) published the first data on phthalate levels in the U.S. population. The highest levels were still less than 1% of the lowest observable effect level in animals, though limited human health data were available. 1,2 However, three recent reports 3–5 (including one in this issue of Epidemiology by Susan Duty and colleagues 3) suggest that phthalates at current population levels may have measurable effects on male reproductive health. “…there is an emerging pattern of adverse semen parameters in the presence of high phthalate levels.” Just as “plastics” was the key word of advice to Dustin Hoffman in The Graduate, “phthalates” may become the key word for environmental epidemiologists in coming years. Phthalate esters are common in PVC plastics, paints and cosmetics. Exposure of laboratory animals as fetuses, pups and adults to phthalate esters can cause reproductive harm. In 1999, the U.S. National Toxicology Program commissioned an expert panel to assess seven phthalate esters and their risk to human reproduction. The candidates included two prime suspects: DEHP (diethylhexyl phthalate) and DBP (dibutyl phthalate). The primary metabolite of DEHP is MEHP (monoethylhexyl phthalate), an antiandrogen that disrupts male reproductive development in animals. Based on the limited scientific literature, which 2 years ago included virtually no human data, the panel identified “serious concern” for neonatal males exposed to DEHP. 6 Preterm babies are highly exposed to DEHP via intravenous and other medical tubing. 7 If phthalates damage male reproduction, preterm male infants are a group likely to experience problems. However, the ability to evaluate this group is limited. It is difficult to assemble a comparison group for a group of infants having extensive medical interventions. Although this remains a vital research question, we will have to look elsewhere for clues about potential reproductive damage from phthalates. In 2000, the CDC released the first population-based data on phthalate exposure. Four phthalate monoesters, including MEHP and MBP (the primary metabolite of DBP), were detectable in nearly all 289 people in an NHANES III sample from 1988–1994 2 and in most of the 1029 people from the NHANES data of 1999. 8 By far the highest levels were for monoethyl phthalate (MEP), a chemical not evaluated by the National Toxicology Program because of its apparent low toxicity in laboratory animals. The extent of human exposure is troubling. Detectable exposures range over two orders of magnitude, and there are practically no data on possible human health effects. In the past few months, the first results from epidemiologic studies have become available. 4–5 It appears that the reproductive effects of phthalates may not be limited to highly exposed animals. In studies from infertility clinics in India 4 and Boston, 5 there is an emerging pattern of adverse semen parameters in the presence of high phthalate levels. “Researchers…should not neglect the possibility that phthalates might affect women as well.” In India, Rozati and colleagues 4 measured phthalate levels in seminal fluid of community controls and patients being treated at an infertility clinic. Phthalates were associated with adverse morphology, sperm head defects and a higher percentage of single-strand deoxyribonucleic acid (DNA) in sperm. These authors used a measure of total phthalate diesters, which does not permit the responsible agent to be specifically identified. Because the treatment protocol was not mentioned, it is possible that these patients may have been exposed to specific phthalates in the course of their medical treatment. If the patients had the same pattern of phthalate exposure as the U.S. population, the main phthalate would be MEP. Among men at a Boston infertility clinic, urinary levels of MEP, but not other phthalates, were associated with adverse integrity of sperm DNA. 5 Although MEP is not known to be genotoxic, 9 taken together these studies suggest the need for further research into its potential to cause DNA damage in sperm. In this issue, Susan Duty and colleagues 3 provide further evidence from the Boston study of infertile men. This new paper reports an association of high urinary MBP levels with low sperm concentration and sperm motility. There was a similar association between MBzP (monobenzylphthalate) and sperm concentration. Surprisingly, no association was observed with MEHP, the phthalate of most concern in the report from the expert panel. Perhaps this is not so unexpected. As the authors note, 3 the animal literature suggests that DEHP (with its metabolite MEHP) has its effects on the male reproductive system only when exposure is before birth. DEHP exposure later in life apparently has no effect. 6 In contrast, DBP can apparently disrupt male reproduction at all stages of life. Thus, the apparent association of MBP (DBP’s active metabolite) with low sperm count and motility in humans is not implausible. Even so, these are all preliminary findings. These studies have been carried out within selected groups of men with known or suspected fertility problems. Both of the analyses by Duty 3,7 have been conducted among men from subfertile couples, so the spectrum of infertility represented is broader than among participants in the study by Rozati, 6 in which all cases had documented low sperm counts. All three studies relied on one sperm sample and one phthalate sample from each subject. As Duty notes, “an accurate measurement of sperm count is difficult using one specimen.” Although urinary phthalate levels appear reproducible from one day to the next, 10 no data are available to assess the long-term reliability of these urinary measures with a short half-life. The stage is now set for more detailed and comprehensive studies of men who are more representative of the general population. Finally, we should not overlook the fact that MBP levels are higher in women than men, 2 perhaps owing to exposures through cosmetics. The animal data suggest that phthalates can also have reproductive effects in females, including impaired uterine function. 11 As researchers attempt to replicate Duty’s findings in men, they should not neglect the possibility that phthalates might affect women as well. About the Author JANE HOPPIN is an environmental epidemiologist at the National Institute of Environmental Health Sciences of the National Institutes of Health. She has conducted studies on the health effects of lead and pesticides. Her current work includes the investigation of human exposure to phthalates, particularly with respect to patterns of exposure.}, number={3}, journal={Epidemiology}, author={Hoppin, J.A.}, year={2003}, pages={259–260} } @article{alavanja_samanic_dosemeci_lubin_tarone_lynch_knott_thomas_hoppin_barker_et al._2003, title={Use of Agricultural Pesticides and Prostate Cancer Risk in the Agricultural Health Study Cohort}, volume={157}, ISSN={0002-9262}, url={http://dx.doi.org/10.1093/aje/kwg040}, DOI={10.1093/aje/kwg040}, abstractNote={The authors examined the relation between 45 common agricultural pesticides and prostate cancer incidence in a prospective cohort study of 55,332 male pesticide applicators from Iowa and North Carolina with no prior history of prostate cancer. Data were collected by means of self-administered questionnaires completed at enrollment (1993-1997). Cancer incidence was determined through population-based cancer registries from enrollment through December 31, 1999. A prostate cancer standardized incidence ratio was computed for the cohort. Odds ratios were computed for individual pesticides and for pesticide use patterns identified by means of factor analysis. A prostate cancer standardized incidence ratio of 1.14 (95% confidence interval: 1.05, 1.24) was observed for the Agricultural Health Study cohort. Use of chlorinated pesticides among applicators over 50 years of age and methyl bromide use were significantly associated with prostate cancer risk. Several other pesticides showed a significantly increased risk of prostate cancer among study subjects with a family history of prostate cancer but not among those with no family history. Important family history-pesticide interactions were observed.}, number={9}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Alavanja, M. C. R. and Samanic, C. and Dosemeci, M. and Lubin, J. and Tarone, R. and Lynch, C.F. and Knott, C. and Thomas, K. and Hoppin, J.A. and Barker, J. and et al.}, year={2003}, month={May}, pages={800–814} } @article{dosemeci_alavanja_rowland_mage_zahm_rothman_lubin_hoppin_sandler_blair_2002, title={A Quantitative Approach for Estimating Exposure to Pesticides in the Agricultural Health Study}, volume={46}, ISSN={1475-3162}, url={http://dx.doi.org/10.1093/annhyg/mef011}, DOI={10.1093/annhyg/mef011}, abstractNote={We developed a quantitative method to estimate long-term chemical-specific pesticide exposures in a large prospective cohort study of more than 58000 pesticide applicators in North Carolina and Iowa. An enrollment questionnaire was administered to applicators to collect basic time- and intensity-related information on pesticide exposure such as mixing condition, duration and frequency of application, application methods and personal protective equipment used. In addition, a detailed take-home questionnaire was administered to collect further intensity-related exposure information such as maintenance or repair of mixing and application equipment, work practices and personal hygiene. More than 40% of the enrolled applicators responded to this detailed take-home questionnaire. Two algorithms were developed to identify applicators' exposure scenarios using information from the enrollment and take-home questionnaires separately in the calculation of subject-specific intensity of exposure score to individual pesticides. The 'general algorithm' used four basic variables (i.e. mixing status, application method, equipment repair status and personal protective equipment use) from the enrollment questionnaire and measurement data from the published pesticide exposure literature to calculate estimated intensity of exposure to individual pesticides for each applicator. The 'detailed' algorithm was based on variables in the general algorithm plus additional exposure information from the take-home questionnaire, including types of mixing system used (i.e. enclosed or open), having a tractor with enclosed cab and/or charcoal filter, frequency of washing equipment after application, frequency of replacing old gloves, personal hygiene and changing clothes after a spill. Weighting factors applied in both algorithms were estimated using measurement data from the published pesticide exposure literature and professional judgment. For each study subject, chemical-specific lifetime cumulative pesticide exposure levels were derived by combining intensity of pesticide exposure as calculated by the two algorithms independently and duration/frequency of pesticide use from the questionnaire. Distributions of duration, intensity and cumulative exposure levels of 2,4-D and chlorpyrifos are presented by state, gender, age group and applicator type (i.e. farmer or commercial applicator) for the entire enrollment cohort and for the sub-cohort of applicators who responded to the take-home questionnaire. The distribution patterns of all basic exposure indices (i.e. intensity, duration and cumulative exposure to 2,4-D and chlorpyrifos) by state, gender, age and applicator type were almost identical in two study populations, indicating that the take-home questionnaire sub-cohort of applicators is representative of the entire cohort in terms of exposure.}, number={2}, journal={The Annals of Occupational Hygiene}, publisher={Oxford University Press (OUP)}, author={Dosemeci, M. and Alavanja, M.C.R. and Rowland, A.S. and Mage, D. and Zahm, S.H. and Rothman, N. and Lubin, J.H. and Hoppin, J.A. and Sandler, D.P. and Blair, A.}, year={2002}, month={Mar}, pages={245–260} } @article{hoppin_yucel_dosemeci_sandler_2002, title={Accuracy of self-reported pesticide use duration information from licensed pesticide applicators in the Agricultural Health Study}, volume={12}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/sj.jea.7500232}, DOI={10.1038/sj.jea.7500232}, abstractNote={Epidemiologists frequently rely on self-reported information regarding a variety of exposures including smoking history, medication use, and occupational exposure because other sources of information are either unavailable or difficult to obtain. One way to evaluate the accuracy of self-reported information is through logic checks using other sources. To assess the quality of the self-reported pesticide product use history of 57,311 licensed pesticide applicators in the Agricultural Health Study (AHS), we compared the self-reported decade of first use and total years of use to the year the pesticide active ingredient was first registered for use. We obtained pesticide active ingredient registration information from the United States Environmental Protection Agency (USEPA) and other publicly available sources for the 52 pesticides on the AHS initial questionnaires administered from 1994 to 1997. Based on the registration year, we assessed 19 pesticides for potential inaccuracies regarding duration of use or decade of first use. When calculating potential total years of use, we did not consider the impact of chemicals being removed from the market, since the possibility for continued use existed. The majority of respondents provided plausible responses for both decade of first use and total duration of use. On average, 1% of the subjects overestimated total possible duration of use, ranging from less than 1% for carbofuran and chlorpyrifos to 5% for imazethapyr. Decade of first use was also reasonably reported, although more subjects did not report decade of first use than duration of use, with an average of 6% of subjects missing decade information for an individual chemical. For subjects who reported a decade of first use, 98% gave plausible responses on average, with overestimates highest for cyanazine, introduced in 1971 (6% reported earlier use), and chlorimuron ethyl, introduced in 1985 (7% reported earlier use). This analysis provided the opportunity to consider only one source of potential overreporting of exposure, and while underreporting may have also occurred, we cannot evaluate its role nor the balance between these potential inaccuracies. While we are unable to validate directly the accuracy of a respondent's use of pesticides, this analysis suggests that participants provide plausible information regarding their pesticide use.}, number={5}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Nature}, author={Hoppin, Jane A and Yucel, Fikri and Dosemeci, Mustafa and Sandler, Dale P}, year={2002}, month={Aug}, pages={313–318} } @article{hoppin_umbach_london_alavanja_sandler_2002, title={Chemical Predictors of Wheeze among Farmer Pesticide Applicators in the Agricultural Health Study}, volume={165}, ISSN={1073-449X 1535-4970}, url={http://dx.doi.org/10.1164/ajrccm.165.5.2106074}, DOI={10.1164/ajrccm.165.5.2106074}, abstractNote={Pesticides may contribute to respiratory symptoms among farmers. Using the Agricultural Health Study, a large cohort of certified pesticide applicators in Iowa and North Carolina, we explored the association between wheeze and pesticide use in the past year. Self-administered questionnaires contained items on 40 currently used pesticides and pesticide application practices. A total of 20,468 applicators, ranging in age from 16 to 88 years, provided complete information; 19% reported wheezing in the past year. Logistic regression models controlling for age, state, smoking, and history of asthma or atopy were used to evaluate associations between individual pesticides and wheeze. Among pesticides suspected to contribute to wheeze, paraquat, three organophosphates (parathion, malathion, and chlorpyrifos), and one thiocarbamate (S-ethyl-dipropylthiocarbamate [EPTC] ) had elevated odds ratios (OR). Parathion had the highest OR (1.5, 95% confidence interval [CI] 1.0, 2.2). Chlorpyrifos, EPTC, paraquat, and parathion demonstrated significant dose–response trends. The herbicides, atrazine and alachlor, but not 2,4-D, were associated with wheeze. Atrazine had a significant dose–response trend with participants applying atrazine more than 20 days/year having an OR of 1.5 (95% CI 1.2,1.9). Inclusion of crops and animals into these models did not significantly alter the observed OR. These associations, though small, suggest an independent role for specific pesticides in respiratory symptoms of farmers.}, number={5}, journal={American Journal of Respiratory and Critical Care Medicine}, publisher={American Thoracic Society}, author={Hoppin, Jane A. and Umbach, David M. and London, Stephanie J. and Alavanja, Michael C. R. and Sandler, Dale P.}, year={2002}, month={Mar}, pages={683–689} } @article{parks_cooper_nylander-french_sanderson_dement_cohen_dooley_treadwell_st.clair_gilkeson_et al._2002, title={Occupational exposure to crystalline silica and risk of systemic lupus erythematosus: A population-based, case-control study in the Southeastern United States}, volume={46}, ISSN={0004-3591 1529-0131}, url={http://dx.doi.org/10.1002/art.10368}, DOI={10.1002/art.10368}, abstractNote={Crystalline silica may act as an immune adjuvant to increase inflammation and antibody production, and findings of occupational cohort studies suggest that silica exposure may be a risk factor for systemic lupus erythematosus (SLE). We undertook this population-based study to examine the association between occupational silica exposure and SLE in the southeastern US.SLE patients (n = 265; diagnosed between January 1, 1995 and July 31, 1999) were recruited from 4 university rheumatology practices and 30 community-based rheumatologists in 60 contiguous counties. Controls (n = 355), frequency-matched to patients by age, sex, and state of residence, were randomly selected from driver's license registries. The mean age of the patients at diagnosis was 39 years; 91% were women and 60% were African American. Detailed occupational and farming histories were collected by in-person interviews. Silica exposure was determined through blinded assessment of job histories by 3 industrial hygienists, and potential medium- or high-level exposures were confirmed through followup telephone interviews. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated by logistic regression.More patients (19%) than controls (8%) had a history of medium- or high-level silica exposure from farming or trades. We observed an association between silica and SLE (medium exposure OR 2.1 [95% CI 1.1-4.0], high exposure OR 4.6 [95% CI 1.4-15.4]) that was seen in separate analyses by sex, race, and at different levels of education.These results suggest that crystalline silica exposure may promote the development of SLE in some individuals. Additional research is recommended in other populations, using study designs that minimize potential selection bias and maximize the quality of exposure assessment.}, number={7}, journal={Arthritis & Rheumatism}, publisher={Wiley}, author={Parks, Christine G. and Cooper, Glinda S. and Nylander-French, Leena A. and Sanderson, Wayne T. and Dement, John M. and Cohen, Philip L. and Dooley, Mary Anne and Treadwell, Edward L. and St.Clair, E. William and Gilkeson, Gary S. and et al.}, year={2002}, month={Jul}, pages={1840–1850} } @article{hoppin_tolbert_taylor_schroeder_holly_2002, title={Potential for selection bias with tumor tissue retrieval in molecular epidemiology studies}, volume={12}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0036134730&partnerID=MN8TOARS}, DOI={10.1016/S1047-2797(01)00250-2}, abstractNote={Molecular epidemiological studies of cancer generally require tumor tissue to evaluate somatic genetic alterations. Frequently this requires retrieval of fixed tissue blocks from hospital pathology archives. The availability of this material may be associated with disease severity, diagnostic practices, hospitals, or risk factors for disease. Tumor material is not available when the diagnosis is made clinically without histological confirmation. These characteristics create difficulties in defining the study base population. Incomplete access to tumor tissue has implications for description of the natural history of disease, estimates of the prevalence of mutation in the population, and evaluation of environmental exposures and critical target gene mutations. Differential diagnostic practices by age groups or across hospitals may create a biased population with respect to potential risk factors. However, this will not bias case-case comparisons unless the mutation of interest is associated both with the exposure of interest and the presence of a tumor block. When subjects with less severe disease are more likely to have biopsies, information regarding the natural history of the disease will be obscured. Investigation of the interaction of environmental agents and critical target gene mutations may be limited if, for example, an environmental agent is associated with a more aggressive form of the disease. Using an ongoing pancreatic cancer case-control study as an example, we discuss the potential for bias associated with differential availability of tumor blocks including consideration of tumor, patient, and hospital characteristics. Due to incomplete retrieval of tissue, the determinants of selection should be described in all studies using tumor tissue, and the implications for generalizability, power, and interpretation of findings in population-based studies should be considered.}, number={1}, journal={Annals of Epidemiology}, author={Hoppin, J.A. and Tolbert, P.E. and Taylor, J.A. and Schroeder, J.C. and Holly, E.A.}, year={2002}, pages={1–6} } @article{coble_hoppin_engel_elci_dosemeci_lynch_alavanja_2002, title={Prevalence of exposure to solvents, metals, grain dust, and other hazards among farmers in the Agricultural Health Study}, volume={12}, ISSN={1559-0631 1559-064X}, url={http://dx.doi.org/10.1038/sj.jea.7500248}, DOI={10.1038/sj.jea.7500248}, abstractNote={Exposures to multiple chemical, physical, and biological agents in agricultural work environments can result in confounding that may obscure or distort risks observed in epidemiologic studies. The Agricultural Health Study (AHS) is a large epidemiology study being conducted to investigate health risks among pesticide applicators and their families. During enrollment in the AHS, questionnaires were administered to over 52,000 licensed pesticide applicators from North Carolina and Iowa, who were mostly farmers. Questions about the frequency of various farming tasks were used to estimate the prevalence of exposure to solvents (25%), metals (68%), grain dusts (65%), diesel exhaust fumes (93%), and other hazards, including exposure to pesticides. Most of the farmers in the AHS reported performing routine maintenance tasks at least once a month, such as painting (63%), welding (64%), and repair of pesticide equipment (58%). The majority of farmers (74% in North Carolina; 59% in Iowa) reported holding nonfarm jobs, of which the most frequent were construction and transportation. The majority of the farmers enrolled in the AHS (55%) also reported that they mixed or applied pesticides on 10 or more days per year. The associations between the use of pesticides and the frequency with which the farmers in the AHS reported performing various types of specific farming activities were assessed to evaluate potential confounding. Confounding risk ratios calculated for these activities suggest that the magnitude of bias due to confounding is likely to be minimal.}, number={6}, journal={Journal of Exposure Science & Environmental Epidemiology}, publisher={Springer Nature}, author={Coble, Joseph and Hoppin, Jane A and Engel, Lawrence and Elci, Omur Cinar and Dosemeci, Mustafa and Lynch, Charles F and Alavanja, Michael}, year={2002}, month={Nov}, pages={418–426} } @article{hoppin_brock_davis_baird_2002, title={Reproducibility of urinary phthalate metabolites in first morning urine samples.}, volume={110}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.02110515}, DOI={10.1289/ehp.02110515}, abstractNote={Phthalates are ubiquitous in our modern environment because of their use in plastics and cosmetic products. Phthalate monoesters--primarily monoethylhexyl phthalate and monobutyl phthalate--are reproductive and developmental toxicants in animals. Accurate measures of phthalate exposure are needed to assess their human health effects. Phthalate monoesters have a biologic half-life of approximately 12 hr, and little is known about the temporal variability and daily reproducibility of urinary measures in humans. To explore these aspects, we measured seven phthalate monoesters and creatinine concentration in two consecutive first-morning urine specimens from 46 African-American women, ages 35-49 years, residing in the Washington, DC, area in 1996-1997. We measured phthalate monoesters using high-pressure liquid chromatography followed by tandem mass spectrometry on a triple quadrupole instrument using atmospheric pressure chemical ionization. We detected four phthalate monoesters in all subjects, with median levels of 31 ng/mL for monobenzyl phthalate (mBzP), 53 ng/mL for monobutyl phthalate (mBP), 211 ng/mL for monoethyl phthalate (mEP), and 7.3 ng/mL for monoethylhexyl phthalate (mEHP). These were similar to concentrations reported for other populations using spot urine specimens. Phthalate levels did not differ between the two sampling days. The Pearson correlation coefficient between the concentrations on the 2 days was 0.8 for mBP, 0.7 for mEHP, 0.6 for mEP, and 0.5 for mBzP. These results suggest that even with the short half-lives of phthalates, women's patterns of exposure may be sufficiently stable to assign an exposure level based on a single first morning void urine measurement.}, number={5}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, Jane A and Brock, John W and Davis, Barbara J and Baird, Donna D}, year={2002}, month={May}, pages={515–518} } @article{hoppin_guzman_tolbert_flagg_2001, title={AGRICULTURAL EXPOSURE HISTORY AMONG AFRICAN-AMERICAN FARMERS IN GEORGIA}, volume={63}, ISSN={1528-7394 1087-2620}, url={http://dx.doi.org/10.1080/15287390151143631}, DOI={10.1080/15287390151143631}, abstractNote={Agricultural exposures differ across the United States by region, calendar time period, and agricultural practice, but most of the published literature focuses on white men in the Midwest. A pilot study was conducted to explore the breadth and diversity of farming practices over time among African-American farmers in Georgia whose exposures may differ in important ways. Using a comprehensive life events calendar questionnaire, 17 male African-American farmers aged 36 to 86 yr residing in southeastern Georgia were interviewed regarding their agricultural history in July 1997. Most men (15/17) reported working on multiple farms in their lifetime; 3 men worked on 5 different farms during their lifetime. These farmers reported using more chemicals during their lifetime than farmers in the Midwest. Used motor oil was the most frequently reported insecticide applied to animals; this apparently common practice has not been described in the literature and should be better understood since its use may result in dermal exposure to polyaromatic hydrocarbons. Better characterization of regionally specific farming history and individual farming practices will facilitate studies of the health effects of farming.}, number={4}, journal={Journal of Toxicology and Environmental Health, Part A}, publisher={Informa UK Limited}, author={Hoppin, Jane A. and Guzman, J. David and Tolbert, Paige E. and Flagg, Elaine W.}, year={2001}, month={Jun}, pages={237–241} } @article{slebos_hoppin_tolbert_holly_brock_zhang_bracci_foley_stockton_mcgregor_et al._2000, title={K-ras and p53 in pancreatic cancer: Association with medical history, histopathology, and environmental exposures in a population-based study}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0033729483&partnerID=MN8TOARS}, number={11}, journal={Cancer Epidemiology Biomarkers and Prevention}, author={Slebos, R.J.C. and Hoppin, J.A. and Tolbert, P.E. and Holly, E.A. and Brock, J.W. and Zhang, R.H. and Bracci, P.M. and Foley, J. and Stockton, P. and McGregor, L.M. and et al.}, year={2000}, pages={1223–1232} } @article{hoppin_flagg_eley_tolbert_jordan_price_2000, title={Letters to the Editor: The validity of self-reported prostrate cancer screening history}, volume={30}, ISSN={0091-7435}, url={http://dx.doi.org/10.1006/pmed.1999.0588}, DOI={10.1006/pmed.1999.0588}, abstractNote={This article charts something of the complicated relation between the sighted reader and the articulation of experiences of blindness by the non-sighted and the becoming-blind. This is achieved, firstly, through an analysis of tropes and folk myths derived from Presocratic myths dealing with conceptions of blindness by the sighted, and secondly through related instances of autobiographical writing by blind subjects that explore or explode such tropes. Throughout the article is an underlying notion of empathic vision, or ‘feeling seeing’. For, alongside an enduring fascination with what the blind ‘see’ (e.g. Sacks, 2003), for the sighted reader there is an allied inquisitiveness concerning what the blind feel.}, number={1}, journal={Preventive Medicine}, publisher={Elsevier BV}, author={Hoppin, Jane and Flagg, E.W. and Eley, J.W. and Tolbert, P.E. and Jordan, T.R. and Price, J.H.}, year={2000}, month={Jan}, pages={78} } @article{hoppin_aro_hu_barry ryan_2000, title={Measurement variability associated with KXRF bone lead measurement in young adults}, volume={108}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034128551&partnerID=MN8TOARS}, number={3}, journal={Environmental Health Perspectives}, author={Hoppin, J.A. and Aro, A. and Hu, H. and Barry Ryan, P.}, year={2000}, pages={239–242} } @article{hoppin_aro_hu_ryan_2000, title={Measurement variability associated with KXRF bone lead measurement in young adults.}, volume={108}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.00108239}, DOI={10.1289/ehp.00108239}, abstractNote={In vivo bone lead measurement using K X-ray fluorescence (KXRF) has been used to estimate long-term lead exposure, especially in adults. Relatively few studies have been conducted on young subjects with this technique. To explore the measurement variability of KXRF bone lead measurements in young subjects, the tibiae of two male cadavers from Boston, Massachusetts, 17 and 20 years of age, were obtained for repeated bone lead measurements. Bone lead concentrations were measured using a grid of nine locations, 1 cm apart, centered at the midpoint of the tibia. Each location was sampled using five 60-min measurements. Measured concentrations ranged from < 0 to 11.8 microg Pb/g bone mineral across a tibia with mean concentrations for the midpoint locations of 0.8 microg Pb/g bone mineral SD = 2.5 and 2.0 microg Pb/g bone mineral (SD = 1.9) for the left and right legs of the younger subject and 3.6 microg Pb/g bone mineral (SD = 2.6) and 6.0 microg Pb/g bone mineral (SD = 3.3) for the left and right legs of the older subject. Although bone lead concentrations did not vary significantly by measurement location in an individual leg, reported measurement uncertainty increased significantly at locations that were 1 cm from the center of the tibia horizontally (p < 0.0001). Symmetry in bone lead concentration between legs was observed for the 17-year-old subject. Potential asymmetry between the left and right legs was suggested for the 20-year-old subject (p = 0.06). These data describe the degree of variability that may be associated with bone lead measurements of young subjects with low bone lead concentrations using a standard spot-source KXRF instrument. Because of the importance of conducting additional research on adolescent lead toxicity, further improvements to the precision of KXRF measurement are needed.}, number={3}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, J A and Aro, A and Hu, H and Ryan, P B}, year={2000}, month={Mar}, pages={239–242} } @article{mirabelli_hoppin_tolbert_herrick_gnepp_brann_2000, title={Occupational exposure to chlorophenol and the risk of nasal and nasopharyngeal cancers among U.S. Men aged 30 to 60}, volume={37}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034029028&partnerID=MN8TOARS}, DOI={10.1002/(SICI)1097-0274(200005)37:5<532::AID-AJIM9>3.0.CO;2-A}, abstractNote={Background Elevated rates of nasal and nasopharyngeal cancers have been associated with wood-related occupational exposures, including chlorophenols, formaldehyde, and wood dust. Methods Occupational information was obtained from 43 nasal carcinoma cases, 92 nasopharyngeal carcinoma cases, and 1909 controls, by interview. Exact conditional logistic regression was used to evaluate the association of these cancers with chlorophenol exposure, estimated from a review of verbatim responses. Results Both nasal and nasopharyngeal cancers were significantly associated with estimated duration of chlorophenol exposure. For nasopharyngeal cancer, elevated risk was observed among those who held jobs assigned medium or high intensity chlorophenol exposure (nexposed=18, OR=1.94, 95% CI=1.03–3.50) and among those with 10+ years in jobs assigned high intensity with high certainty (nexposed=3, OR=9.07, 95% CI=1.41–42.9). Controlling for estimated formaldehyde and wood dust exposure did not alter these findings, as much of the estimated chlorophenol exposure was among machinists. Conclusions These findings support the hypothesis that occupational exposure to chlorophenol is a risk factor for nasal and nasopharyngeal cancer, although the role of machining-related exposures warrants further assessment. Am. J. Ind. Med. 37:532–541, 2000. © 2000 Wiley-Liss, Inc.}, number={5}, journal={American Journal of Industrial Medicine}, author={Mirabelli, M.C. and Hoppin, J.A. and Tolbert, P.E. and Herrick, R.F. and Gnepp, D.R. and Brann, E.A.}, year={2000}, pages={532–541} } @article{hoppin_tolbert_holly_brock_korrick_altshul_zhang_bracci_burse_needham_2000, title={Pancreatic cancer and serum organochlorine levels}, volume={9}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0034003536&partnerID=MN8TOARS}, number={2}, journal={Cancer Epidemiology Biomarkers and Prevention}, author={Hoppin, J.A. and Tolbert, P.E. and Holly, E.A. and Brock, J.W. and Korrick, S.A. and Altshul, L.M. and Zhang, R.H. and Bracci, P.M. and Burse, V.W. and Needham, L.L.}, year={2000}, pages={199–205} } @article{garabedian_hoppin_tolbert_herrick_brann_1999, title={Occupational chlorophenol exposure and non-Hodgkin's lymphoma}, volume={41}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032943982&partnerID=MN8TOARS}, number={4}, journal={Journal of Occupational and Environmental Medicine}, author={Garabedian, M.J. and Hoppin, J.A. and Tolbert, P.E. and Herrick, R.F. and Brann, E.A.}, year={1999}, pages={267–272} } @article{hoppin_tolbert_dana flanders_zhang_daniels_ragsdale_brann_1999, title={Occupational risk factors for sarcoma subtypes}, volume={10}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032928122&partnerID=MN8TOARS}, number={3}, journal={Epidemiology}, author={Hoppin, J.A. and Tolbert, P.E. and Dana Flanders, W. and Zhang, R.H. and Daniels, D.S. and Ragsdale, B.D. and Brann, E.A.}, year={1999}, pages={300–306} } @article{blanck_tolbert_hoppin_1999, title={Patterns of genetic alterations in pancreatic cancer: A pooled analysis}, volume={33}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0032939249&partnerID=MN8TOARS}, DOI={10.1002/(SICI)1098-2280(1999)33:2<111::AID-EM3>3.0.CO;2-F}, abstractNote={Both K-ras and p53 gene mutations are found commonly in pancreatic tumors. Analysis of the mutational patterns may provide insight into disease etiology. To further describe the mutational patterns of pancreatic cancer and to assess the evidence to date, we performed a pooled analysis of the published data on genetic mutations associated with pancreatic ductal adenocarcinoma. We included data from studies that evaluated point mutations in the two genes most studied in pancreatic cancer, K-ras and p53. A majority of the 204 tumors had mutations in at least one gene, with 29% having both K-ras and p53 mutations, 39% with K-ras mutation alone, and 16% having p53 mutation alone. Sixteen percent of tumors lacked mutation in either gene. K-ras mutations were present in high frequencies in all tumor grades (>69%). A statistically significant trend was observed for p53 mutation with higher tumor grade (P = 0.04). For K-ras, G2 and G3 grades, combined, had notably higher prevalences of mutation than G1 (P = 0.004). CGT mutations in K-ras codon 12 were marginally associated with lower tumor grade (P for trend = 0.09), and these tumors were somewhat less likely to have a p53 mutation than tumors with other K-ras mutations (P = 0.06). In the 59 K-ras+/p53+ tumors, 64% had the same type of mutation (transition or transversion) in both genes, suggesting a common mechanism. The mutational pattern of p53 in pancreatic cancer is similar to bladder cancer, another smoking-related cancer, but not to lung cancer. Analyses of molecular data, such as that performed here, present new avenues for epidemiologists in the study of the etiology of specific cancers. Environ. Mol. Mutagen. 33:111–122, 1999 © 1999 Wiley-Liss, Inc.}, number={2}, journal={Environmental and Molecular Mutagenesis}, author={Blanck, H.M. and Tolbert, P.E. and Hoppin, J.A.}, year={1999}, pages={111–122} } @article{hoppin_tolbert_herrick_freedman_ragsdale_horvat_brann_1998, title={Occupational Chlorophenol Exposure and Soft Tissue Sarcoma Risk among Men Aged 30-60 Years}, volume={148}, ISSN={0002-9262 1476-6256}, url={http://dx.doi.org/10.1093/aje/148.7.693}, DOI={10.1093/aje/148.7.693}, abstractNote={To evaluate the association of chlorophenol exposure with soft tissue sarcoma risk independent of phenoxyherbicide exposure, the authors analyzed data from the Selected Cancers Study, a population-based case-control study that included 295 male soft tissue sarcoma cases, aged 32-60 years, from eight population-based cancer registries and 1,908 male controls. Chlorophenol exposure was assigned using both an intensity and a confidence estimate by an industrial hygienist based on verbatim job descriptions. Seventeen percent of the jobs rated as high intensity involved wood preservation, while 82% involved cutting oils. Soft tissue sarcoma risk, modeled using conditional logistic regression, was significantly associated with ever having high-intensity chlorophenol exposure (odds ratio = 1.79, 95% confidence interval 1.10-2.88). A duration-response trend was evident among more highly exposed subjects (p for trend < 0.0001). For subjects with 10 or more years of substantial exposure, the odds ratio was 7.78 (95% confidence interval 2.46-24.65). These results suggest that chlorophenol exposure independent of phenoxyherbicides may increase the risk of soft tissue sarcoma. Because of the large number of machinists in the exposed group and the complex composition of cutting fluids, it is possible that another exposure involved in machining is responsible for the observed excess risk.}, number={7}, journal={American Journal of Epidemiology}, publisher={Oxford University Press (OUP)}, author={Hoppin, J. A. and Tolbert, P. E. and Herrick, R. F. and Freedman, D. S. and Ragsdale, B. D. and Horvat, K. R. and Brann, E. A.}, year={1998}, month={Oct}, pages={693–703} } @article{hoppin_tolbert_flagg_blair_zahm_1998, title={Use of a life events calendar approach to elicit occupational history from farmers}, volume={34}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0031709557&partnerID=MN8TOARS}, DOI={10.1002/(SICI)1097-0274(199811)34:5<470::AID-AJIM7>3.0.CO;2-U}, abstractNote={Background Precise and valid exposure assessment is generally the primary challenge in retrospective occupational epidemiology studies, particularly when the only available method for exposure characterization is a personal interview. Agricultural workers may represent a particular challenge; for example, whereas many farmers have worked from childhood at the same location, raising the same crops and animals, they may have used different equipment, chemicals, and protective gear over time. One method to assist in recall is the "life events calendar," a cognitive tool based on the subject's own life history to help anchor occupational activities in time. Methods Unstructured interviews of farmers, focus groups, and pilot interviews among rural men, primarily African-Americans, were conducted to create a questionnaire for obtaining farm history information within the context of personal life events. Results Farmers used both personal events and national events (as well as events relating directly to farming) to recall their activities. These subjects had extensive history of farming (10–75 years) and chemical use (median lifetime chemicals = 13). Conclusion The life events calendar provided a useful tool to facilitate the recall of a lifetime of agricultural activity. Life events calendars are useful additions to the tools available for retrospective occupational exposure assessment. Am. J. Ind. Med. 34:470-476, 1998. © 1998 Wiley-Liss, Inc.}, number={5}, journal={American Journal of Industrial Medicine}, author={Hoppin, J.A. and Tolbert, P.E. and Flagg, E.W. and Blair, A. and Zahm, S.H.}, year={1998}, pages={470–476} } @article{hoppin_aro_hu_ryan_1997, title={In Vivo Bone Lead Measurement in Suburban Teenagers}, volume={100}, ISSN={0031-4005 1098-4275}, url={http://dx.doi.org/10.1542/peds.100.3.365}, DOI={10.1542/peds.100.3.365}, abstractNote={Objective. Bone represents a biologically active long-term storage site for lead, and bone lead data on teenagers are limited. Therefore, this study was designed to identify the distribution of bone lead in a teenage population and to explore the environmental and demographic factors associated with bone lead concentrations in young, nonoccupationally exposed subjects. Design. A cross-sectional study of bone lead levels in high school students. Participants. A total of 168 students at a suburban Boston high school. Subjects (90 boys, 78 girls) ranged in age from 13.5 to 19 years and included 40% nonwhite minorities. Of the 168 subjects, 45 lived in homes constructed before 1960. None of the participants reported a history of lead poisoning. Outcome Measures. Tibial bone lead concentrations were measured in vivo for 60 minutes using K x-ray fluorescence. Lead exposure information was obtained by self-administered questionnaire. Results. Point estimates of bone lead levels ranged from −7.15 to 14.23 μg lead/g bone mineral (μg/g), (mean, 4.0 μg/g; standard deviation, 4.4 μg/g). The reported measurement uncertainties accompanying each of the point estimates ranged from 2.56 to 9.01 μg/g (mean, 3.9 μg/g; standard deviation, 1.0 μg/g). Bone lead levels were not associated with the demographic factors of age, sex, or race. Additionally, current home conditions (housing age, traffic level) were not predictive of bone lead levels, even though these factors were predictive of in-home lead concentrations. Conclusions. These results demonstrate that although bone lead levels are measurable in this age group, the common predictors of blood and bone lead concentrations are not explanatory for bone lead levels.}, number={3}, journal={PEDIATRICS}, publisher={American Academy of Pediatrics (AAP)}, author={Hoppin, J. A. and Aro, A. and Hu, H. and Ryan, P. B.}, year={1997}, month={Sep}, pages={365–370} } @article{hoppin_elreedy_ryan_1997, title={Validation of a Self-Administered Lead Exposure Questionnaire among Suburban Teenagers}, volume={74}, ISSN={0013-9351}, url={http://dx.doi.org/10.1006/enrs.1997.3738}, DOI={10.1006/enrs.1997.3738}, abstractNote={Teenagers represent a unique population in which to evaluate lead exposure. A self-administered questionnaire was developed to evaluate the current and historic lead exposures of teenagers. This work evaluates the exposure questionnaire for both its ability to predict lead exposure and the accuracy of the teenage respondents. Subjects received the survey at school and were instructed to get assistance from their parents in questionnaire completion. Environmental samples (dust, soil, and water) were collected from 30 suburban Boston homes to evaluate the questionnaire's predictiveness. To evaluate the accuracy of subjects' responses, independent information about housing was obtained. The questionnaire was effective in identifying predictors of dust and soil lead levels, but not for water lead levels. Fine dust lead loading (< 150 microns) varied significantly among the six housing age categories (pre-1940, 1940-1949, 1950-1959, 1960-1969, 1970-1979, and > 1979) and traffic levels. Fine dust lead concentrations varied significantly with decade of housing construction. Mean soil lead levels varied significantly among housing age categories, traffic levels, and exterior construction materials. For the important predictors, there was excellent agreement between the teenagers' self-report and confirmatory information. For housing age categories, the observed agreement was 69%; for traffic level, the observed agreement was 88%. These results illustrate that questionnaires continue to be useful in evaluating home lead levels even in suburban homes and that teenagers are accurate respondents.}, number={1}, journal={Environmental Research}, publisher={Elsevier BV}, author={Hoppin, Jane A. and Elreedy, Salma and Ryan, P.Barry}, year={1997}, pages={1–10} } @article{hoppin_1996, title={Bone lead levels and delinquent behavior}, volume={275}, ISSN={0098-7484 1538-3598}, url={http://dx.doi.org/10.1001/jama.275.22.1727b}, DOI={10.1001/jama.275.22.1727b}, number={22}, journal={JAMA: The Journal of the American Medical Association}, publisher={American Medical Association (AMA)}, author={Hoppin, J. A.}, year={1996}, month={Jun}, pages={1727b–1727} } @article{bone lead levels and delinquent behavior [3]_1996, volume={275}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-15844425580&partnerID=MN8TOARS}, DOI={10.1001/jama.275.22.1725}, abstractNote={

To the Editor.

—Contrary to the results of the study by Dr Needleman and colleagues,1after a 3-decade follow-up study of more than 69 of 110 (63%) of my former patients whose blood lead levels were between 4.83 and 22.68 μmol/L (100 and 470 μg/dL), I have yet to encounter the predicted outcome. Eighty percent of this cohort of inner-city black subjects graduated from high school, a third entered college, and 6 have already obtained 1 or 2 degrees. Three of the college graduates had symptoms of incipient encephalopathy before they received chelation therapy.2 Needleman et al leave several questions unanswered. Has the x-ray fluorescence (XRF) technique been validated on children with known lead poisoning (ie, lead concentrations in blood of 3.86 μmol/L [80 μg/dL] or more)? Their study lacks a proper control population. We have lead in our red blood cells at the time of birth, and}, number={22}, journal={Journal of the American Medical Association}, year={1996}, pages={1725–1728} } @article{hoppin_ryan_hu_aro_1996, title={Bone lead levels and delinquent behavior.}, volume={275}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0030580911&partnerID=MN8TOARS}, number={22}, journal={JAMA : the journal of the American Medical Association}, author={Hoppin, J.A. and Ryan, P.B. and Hu, H. and Aro, A.C.}, year={1996} } @article{hauser_elreedy_hoppin_christiani_1995, title={Airway obstruction in boilermakers exposed to fuel oil ash. A prospective investigation.}, volume={152}, ISSN={1073-449X 1535-4970}, url={http://dx.doi.org/10.1164/ajrccm.152.5.7582280}, DOI={10.1164/ajrccm.152.5.7582280}, abstractNote={We prospectively investigated the lower airway response in boilermakers overhauling an oil-powered boiler. We studied 26 male boilermakers with a mean age (SD) of 43.3 (8.6) yr. Pre-exposure spirometry and methacholine challenge tests were performed before beginning the boiler overhaul; postexposure tests were performed after approximately 4 wk of work on the boiler. Exposure to particulates with an aerodynamic diameter of 10 microns and smaller (PM10) and respirable vanadium dust were estimated using daily work diaries and a personal sampling device for respirable particles. Using these estimates, we calculated average and peak exposure between pre- and postexposure tests for each subject. The average PM10 concentration ranged from 1.44 to 6.69 mg/m3, with a mean (SD) of 3.22 (1.42) mg/m3; the average vanadium concentration ranged from 2.2 to 31.3, with a mean (SD) of 12.2 (9.1) micrograms/m3. The mean postexposure fall in FEV1 was 140 +/- 160 ml (p < 0.01); 24 of 26 subjects had a drop in FEV1. For each subject, the adjusted change in FEV1 (delta FEV1.adj) was calculated by dividing the change in FEV1 by the average of the pre- and postexposure FEV1 values. The delta FEV1.adj was regressed, controlling age and current smoking status, on average and peak exposure to both PM10 and vanadium. There was a dose-response relationship between average and peak PM10 exposure and delta FEV1.adj: beta = -0.91% per mg/m3, p = 0.08 and beta = -1.03% per mg/m3, p = 0.03, respectively. However, there was no relationship between delta FEV1.adj and respirable vanadium dust concentration. Furthermore, there was no postexposure change in nonspecific airway responsiveness. In summary, we found a significant fall in FEV1 and a dose-response relationship between delta FEV1.adj and average and peak PM10 exposure.(ABSTRACT TRUNCATED AT 250 WORDS)}, number={5}, journal={American Journal of Respiratory and Critical Care Medicine}, publisher={American Thoracic Society}, author={Hauser, R and Elreedy, S and Hoppin, J A and Christiani, D C}, year={1995}, month={Nov}, pages={1478–1484} } @article{hauser_elreedy_hoppin_christiani_1995, title={Airway obstruction in boilermakers exposed to fuel oil ash: A prospective investigation}, volume={152}, url={http://www.scopus.com/inward/record.url?eid=2-s2.0-0028806709&partnerID=MN8TOARS}, number={5 I}, journal={American Journal of Respiratory and Critical Care Medicine}, author={Hauser, R. and Elreedy, S. and Hoppin, J.A. and Christiani, D.C.}, year={1995}, pages={1478–1484} } @article{hauser_elreedy_hoppin_christiani_1995, title={Upper airway response in workers exposed to fuel oil ash: nasal lavage analysis.}, volume={52}, ISSN={1351-0711}, url={http://dx.doi.org/10.1136/oem.52.5.353}, DOI={10.1136/oem.52.5.353}, abstractNote={OBJECTIVES--Among other constituents, fuel oil ash contains vanadium pentoxide, a known respiratory irritant. Exposure to ambient vanadium pentoxide dust has been shown to produce irritation of the eyes, nose, and throat. The usefulness of nasal lavage in detecting an inflammatory response to exposure to fuel oil ash among 37 boilermakers and utility workers was investigated. METHODS--A baseline lavage was performed on the morning of the first day back to work after an average of 114 days away from work (range 36 hours to 1737 days). A lavage was performed after exposure on the morning three days after the baseline lavage. Exposure to respirable particulate matter of diameter < or = 10 microns (PM10) and respirable vanadium dust were estimated with daily work diaries and a personal sampling device for respirable particulates. These estimates were made for each subject on each workday during the three days between lavages. For each subject, the adjusted change in polymorphonuclear cells was calculated by dividing the change in polymorphonuclear cell counts by the average of the counts before and after exposure. The association between the adjusted polymorphonuclear cell counts and exposure was assessed with multiple linear regression, adjusted for age and current smoking. RESULTS--Personal sampling (one to 10 hour time weighted average) showed a range of PM10 concentrations of 50 to 4510 micrograms/m3, and respirable vanadium dust concentration of 0.10 to 139 micrograms/m3. In smokers the adjusted polymorphonuclear cell count was not significantly different from zero (-0.1%, P > 0.5), but in nonsmokers it was significantly greater than zero (+50%, P < 0.05). In both non-smokers and smokers, there was considerable variability in adjusted polymorphonuclear cell counts and a dose-response relation between these adjusted cell counts and either PM10 or respirable vanadium dust exposure could not be found. CONCLUSION--A significant increase in polymorphonuclear cells in non-smokers but not smokers was found. This suggests that in non-smokers, exposure to fuel oil ash is associated with upper airway inflammation manifested as increased polymorphonuclear cell counts. The lack of an increase in polymorphonuclear cells in smokers may reflect either a diminished inflammatory response or may indicate that smoking masks the effect of exposure to fuel oil ash.}, number={5}, journal={Occupational and Environmental Medicine}, publisher={BMJ}, author={Hauser, R and Elreedy, S and Hoppin, J A and Christiani, D C}, year={1995}, month={May}, pages={353–358} } @article{hoppin_aro_williams_hu_ryan_1995, title={Validation of K-XRF bone lead measurement in young adults.}, volume={103}, ISSN={0091-6765 1552-9924}, url={http://dx.doi.org/10.1289/ehp.9510378}, DOI={10.1289/ehp.9510378}, abstractNote={K-X-ray fluorescence (K-XRF) is a useful tool for assessing environmental exposure to lead in occupationally exposed individuals and older adults. This study explores the possibility of using this technique on young adults with low environmental lead exposure. Twenty-three college students, aged 18-21 years, were recruited for 2 hr of bone lead measurement. Bone lead measurements were taken from the mid-shaft tibia for periods of 30 or 60 min. In the analysis, 30-min measurements were combined so that each subject had the equivalent of two 60-min measurements. The average concentration of two bone lead measurements in this population ranged from -1.5 to 8.2 micrograms Pb/g bone mineral, with a mean of 3.0 micrograms Pb/g bone mineral. In a one sample t-test, this mean was significantly different from 0 (p < 0.0001). A linear trend with age was detected despite the small age range of our population. By doubling the sampling time, the reported measurement uncertainty decreased by a factor of 1.5, resulting in uncertainty estimates below the mean bone lead estimates. Power calculations using the observed variance estimates suggest that with 80% power, differences in bone lead concentration of 2-3 micrograms Pb/g bone mineral can be identified in groups of 100 or smaller. Due to the large within-person variation in young adults, K-XRF may not yet be a useful diagnostic tool for individual subjects, but it may be of great use to environmental scientists trying to characterize long-term lead exposure and dose in the general population or specific subpopulations.}, number={1}, journal={Environmental Health Perspectives}, publisher={Environmental Health Perspectives}, author={Hoppin, J A and Aro, A C and Williams, P L and Hu, H and Ryan, P B}, year={1995}, month={Jan}, pages={78–83} }